Antiatherosclerotic ureas and thioureas

ABSTRACT

This invention is concerned with ureas and thioureas which may be represented by the formula: ##STR1## wherein X represents at least one substituent selected from the group consisting of (C 1  -C 4 )alkyl, (C 1  -C 4 )alkenyl, (C 1  -C 4 )alkynyl, phenoxy, mercapto, amino, (C 1  -C 4 )alkylamino, di-(C 1  -C 4 )alkylamino, halo, trihalomethyl, (C 1  -C 4 )alkanoyl, benzoyl, (C 1  -C 4 )alkanamido, haloacetamido, nitro, cyano, carboxy, (C 1  -C 4 )carboalkoxy, carbamoyl, sulfamyl, methylenedioxy, phenyl, orthophenylene, tolyl, benzyl, halobenzyl, methylbenzyl; Y is selected from the group consisting of oxygen and sulfur; R 1  and R 2  are different and are independently selected from the group consisting of (C 4  -C 12 )alkyl, (C 4  -C 12 )alkenyl, (C 4  -C 12 )alkynyl, (C 4  -C 12 )cycloalkyalkyl, (C 7  -C 14 )aralkyl, and (C 7  -C 14 )aralkyl in which an aromatic ring bears at least one substituent selected from the group consisting of (C 1  -C 10 )alkyl, (C 1  -C 10 )alkoxy, phenoxy, benzyloxy, methylenedioxy, (C 1  -C 4 )alkylthio, phenyl, halo, trihalomethyl, adamantyl, (C 1  -C 4 )carboalkoxy, and nitro.

BACKGROUND OF THE INVENTION

This application is a division of my copending application Ser. No. 737,360, filed May 23, 1985,now U.S. Pat. No. 4,623,662, which is a continuation-in-part of my abandoned application Ser. No. 515,321, filed July 19, 1983, which in turn is a continuation-in-part of my abandoned application Ser. No. 342,692, filed Jan. 26, 1982.

This invention relates to new urea and thiourea compounds useful as pharmaceutical agents. The novel compounds of the present invention are antiatherosclerotic agents capable of ameliorating atherosclerosis by counteracting the formation or development of atheromatous lesions in the arterial wall of mammals. The invention also relates to the chemical synthesis of the novel compounds disclosed herein. In addition, the invention pertains to novel pharmaceutical compositions for the utilization of these compounds in the treatment of disease in mammals. Further, the invention contemplates methods for treating atherosclerosis in a manner designed to prevent, arrest, or reverse the course of the disease.

A variety of urea and thiourea compounds can be found in the literature, for example, in J. Med. Chem., 18: 1024 (1975); Chem. Absts., 95: 6758m (1981) and 91: 74631g (1979); U.S. Pat. Nos. 2,688,039; 3,335,142; 3,856,952; 3,903,130; 4,252,957; 4,405,644; and 4,460,607. The compounds found in the literature are disclosed as being useful herbicides, plant growth regulators, bactericides, pesticides, fungicides, algaides, photographic sensitizers, antihelmintics, sympatholytics, and antivirals. Those urea compounds found in U.S. Pat. Nos. 4,405,644 and 4,460,607 are disclosed as useful in inhibiting lipid absorption. There are, however, no literature references disclosing the urea and thiourea compounds of the present invention or their use in the treatment of atherosclerosis or hyperlipidemia.

Atherosclerosis is a form of arteriosclerosis characterized by lipid accumulation in and thickening of the arterial walls of both medium- and large-sized arteries. Arterial walls are thereby weakened, and the elasticity and effective internal size of the artery is decreased. Atherosclerosis is the most common cause of ischemic heart disease and is of great medical importance since the occlusion of medium- and large-sized arteries diminishes the supply of blood to vital organs such as the heart muscles and the brain. The sequelae to atherosclerosis include ischemic heart disease, heart failure, lifethreatening arrythmias, senility, and stroke.

The fact that cholesterol is a major component of atherosclerotic lesions or plaques has been known for more than 100 years. Various researchers have studied the role of cholesterol in lesion formation and development and also, more importantly, whether lesion formation can be prevented or lesion development arrested or reversed. Atheromatous lesions have now been shown [Adams, et al., Atherosclerosis, 13: 429 (1974)] to contain a greater quantity of esterified as opposed to unesterified cholesterol than the surrounding undiseased arterial wall. The intracellular esterification of cholesterol with fatty acids is catalyzed by the enzyme Fatty acyl CoA:cholesterol acyl transferase or ACAT, and the accumulation and storage of cholesteryl esters in the arterial wall is associated with increased activity of this enzyme [Hashimoto and Dayton, Atherosclerosis, 28: 447 (1977)]. In addition, cholesteryl esters are removed from cells at a slower rate than unesterified cholesterol [Bondjers and Bjorkerud, Atherosclerosis, 15: 273 (1972) and 22: 379 (1975)]. Thus, inhibition of the ACAT enzyme would diminish the rate of cholesterol esterification, decrease the accumulation and storage of cholesteryl esters in the arterial wall, and prevent or inhibit the formation and development of atheromatous lesions. The compounds of the present invention are very potent inhibitors of the ACAT enzyme. Thus, these compounds are useful for controlling and reducing the cholesteryl ester content of mammalian arterial walls and decreasing the accumulation and storage of cholesterol in the arterial walls of mammals. Further, the compounds of this invention inhibit the formation or development of atherosclerotic lesions in mammals.

The evidence that hyperlipidemia is one of the factors involved in coronary heart disease is very impressive. A most important study carried out in Framingham, Massachusetts in over 5,000 persons for more than 12 years established a correlation between high concentrations of blood cholesterol and increased risk of heart attack. Although the causes of coronary artery disease are multiple, one of the most constant factors has been the elevated concentration of lipids in the blood plasma. A combined elevation of cholesterol and triglycerides has been shown to carry the highest risk of coronary heart disease. The majority of patients with ischemic heart disease or peripheral vascular disease were found to have hyperlipoproteinemia, involving very low-density and/or low-density lipoproteins.

I have now found that certain members of this class of compounds can safely and effectively lower serum lipids in warm-blooded animals. Such action on serum lipids is considered to be very useful in the treatment of atherosclerosis. For some time, it has been considered desirable to lower serum-lipid levels and to correct lipoprotein imbalance in mammals as a preventive measure against atherosclerosis. The compounds of the present invention do not act by blocking late stages of cholesterol biosynthesis and thus do not produce accumulation of intermediates such as desmosterol, as equally undesirable as cholesterol itself. Compounds with the combination of therapeutically favorable characteristics possessed by those of the present invention can be safely administered to warm-blooded mammals for the treatment of hyperlipidemic and atherosclerotic states found in patients with or prone to heart attacks, to peripheral or cerebral vascular disease, and to stroke.

The compounds of this invention exhibit antiatherosclerotic activity, and the invention should not be construed as limited to any particular mechanism of antiatherosclerotic action.

SUMMARY OF THE INVENTION

This invention relates to new urea and thiourea compounds, their preparation, pharmaceutical compositions containing them, and their use in the treatment of atherosclerosis. More particularly, it is generically concerned with ureas and thioureas which may be represented by Formula I: ##STR2## wherein X represents at least one substituent selected from the group consisting of (C₁ -C₄)alkyl, (C₁ -C₄)alkenyl, (C₁ -C₄)alkynyl, phenoxy, mercapto, amino, (C₁ -C₄)alkylamino, di-(C₁ -C₄)alkylamino, halo, trihalomethyl, (C₁ -C₄)alkanoyl, benzoyl, (C₁ -C₄)alkanamido haloacetamido, nitro, cyano, carboxy, (C₁ -C₄)carboalkoxy, carbamoyl, sulfamyl, methylenedioxy, phenyl, orthophenylene, tolyl, benzyl, halobenzyl, methylbenzyl, and the group: ##STR3## Y is selected from the group consisting of oxygen and sulfur; R₁ is selected from the group consisting of (C₄ -C₁₂)alkyl, (C₄ -C₁₂)alkenyl, (C₄ -C₁₂)alkynyl, (C4-C12)cycloalkylalkyl, (C₇ -C₁₄)aralkyl, and (C₇ -C₁₄)aralkyl in which an aromatic ring bears at least one substituent selected from the group consisting of (C₁ -C₁₀)alkyl, (C₁ C₁₀)alkoxy, phenoxy, benzyloxy, methylenedioxy, (C₁ -C₄)alkylthio, phenyl, halo, trihalomethyl, adamantyl, (C₁ -C₄)carboalkoxy, and nitro; and R₂ is not identical to R₁ and is selected from the group consisting of (C₄ -C₁₂)alkyl, (C₄ -C₁₂)alkenyl, (C₄ -C₁₂)alkynyl, (C₄ -C₁₂)cycloalkylalkyl, (C₇ -C₁₄)aralkyl, and (C₇ -C₁₄)aralkyl in which an aromatic ring bears at least one substituent selected from the group consisting of (C₁ -C₁₀)alkyl, (C₁ -C₁₀)alkoxy, phenoxy, benzyloxy, methylenedioxy, (C₁ C₄)alkylthio, phenyl, halo, trihalomethyl, adamantyl, (C₁ -C₄)carboalkoxy, nitro, and A--Z wherein A is selected from the group consisting of (C₂ -C₁₀)alkylene, (C₂ -C₁₀)alkenylene, and (C₂ -C₁₀)alkynylene and Z is selected from the group consisting of carboxy, (C₁ -C₄)carboalkoxy, carbamoyl, (C₁ -C₄)perfluoroalkyl, (tri(C₁ -C₄)alkyl)silyl, cyano, halo, mercapto, (C₁ -C₄)alkylthio, hydroxy, (C₁ -C₄)alkoxy, methylsulfonyloxy, (C₁ -C₄)alkoxy, thienyl, furyl, and pyrimidinyl.

A preferred subgeneric group of ureas and thioureas with which this invention is concerned may be represented by Formula II: ##STR4## wherein X represents at least one substituent selected from the group consisting of (C₁ -C₄)alkyl (C₁ -C₄)alkenyl (C₁ -C₄)alkynyl, phenoxy, mercapto, amino, (C₁ -C₄)alkylamino, di-(C₁ -C₄)alkylamino, halo, trihalomethyl, (C₁ -C₄)alkanoyl, benzoyl, (C₁ -C₄)alkanamido, haloacetamido, nitro, cyano, carboxy, (C₁ -C₄)carboalkoxy, carbamoyl, sulfamyl, methylenedioxy, phenyl, orthophenylene, tolyl, benzyl, halobenzyl, methylbenzyl; Y is selected from the group consisting of oxygen and sulfur; R₁ and R₂ are different and are independently selected from the group consisting of (C₄ -C₁₂)alkyl, (C₄ -C₁₂)alkenyl, (C₄ -C₁₂)alkynyl, (C₄ -C₁₂)cycloalkylalkyl, (C₇ -C₁₄)aralkyl, and (C₇ -C₁₄)aralkyl in which an aromatic ring bears at least one substituent selected from the group consisting of (C₁ -C₁₀)alkyl, (C₁ -C₁₀)alkoxy, phenoxy, benzyloxy, methylenedioxy, (C₁ -C₄)alkylthio, phenyl, halo, trihalomethyl, adamantyl, (C₁ -C₄)carboalkoxy, and nitro.

Preferred embodiments of the invention represented by Formula II are those in which Y is oxygen. More preferred are those in which X represents at least one (C₁ -C₄)alkyl or halo substituent, R₁ is (C₇ -C₁₄)aralkyl or substituted (C₇ -C₁₄)aralkyl, and R₂ is (C₄ -C₁₂)alkyl. The most preferred are those in which X represents at least one methyl, chloro, or fluoro substituent.

Preferred specific embodiments involve trisubstituted ureas, for example:

1-Benzyl-1-(n-butyl)-3-(2,4-dimethylphenyl)urea

1-Benzyl-1-(1,2-diphenylethyl)-3-(2,4-dimethylphenyl)urea

1-(2-Fluorobenzyl)-1-(2-methoxybenzyl)-3-(2,4-dimethylphenyl)urea

1-(n-Butyl)-1-(4-hexyloxybenzyl)-3-(2,4-dimethylphenyl)urea

1-Benzyl-1-(4-n-butylbenzyl)-3-(2,4-dimethylphenyl)urea

1-Benzyl-1-(4-n-butylbenzyl)-3-(2,4,6-trimethylphenyl)urea

1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4-dimethylphenyl)urea

1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4,5-trimethylphenyl)urea

1-(n-Heptyl)-1-(4-butyloxybenzyl)-3-(2,4-dimethylphenyl)urea

1-(n-Heptyl)-1-(4-butyloxybenzyl)-3-(2,4,5-trimethylphenyl)urea

1-Benzyl-1-(4-butyloxybenzyl)-3-(2,4-dimethylphenyl)urea

1-Benzyl-1-(4-butyloxybenzyl)-3-(2,4,5-trimethylphenyl)urea

1-Benzyl-1-(4-n-butylbenzyl)-3-(2,4,5-trimethylphenyl)urea

1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-(2,4,6-trichlorophenyl)urea

1-Benzyl-1-(4-n-butoxybenzyl)-3-(2,4,6-trichlorophenyl)urea

1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4,6-trichlorophenyl)urea

1-Benzyl-1-(4-n-butylbenzyl)-3-(2-methyl-4-chlorophenyl)urea

1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-(2,4-difluorophenyl)urea

1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-(2-methyl-4-chlorophenyl)urea

1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2-methyl-4-chlorophenyl)urea

1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4-difluorophenyl)urea

1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2-methylphenyl)urea

1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4-dimethylphenyl)urea

1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-(2,4,6-trichlorophenyl)urea

1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-(2-methyl-4-chlorophenyl)urea

1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-(2,4-difluorophenyl)urea

1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphenyl)ethyl]-3-(2,4-difluorophenyl)urea

1-Benzyl-1-(4-n-butoxybenzyl)-3-(2,4-difluorophenyl)urea

1-(2-Furanylmethyl)-1-heptyl-3-(2,4,5-trimethylphenyl)urea

1-(2-Furanylmethyl)-1-heptyl-3-(2,4,6-trichlorophenyl)urea

1-Heptyl-1-(2-thienylmethyl)-3-(2,4,5-trimethylphenyl)urea

1-Heptyl-1-(2-thienylmethyl)-3-(2,4,6-trichlorophenyl)urea

1-[(4-Butoxyphenyl)methyl]-1-(2-thienylmethyl)-3-(2,4,5-trimethylphenyl)urea

1-[(4-Butylphenyl)methyl]-1-(6-cyanohexyl)-3-(2,4,5-trimethylphenyl)urea

1-[(4-Butylphenyl)methyl]-1-(6-chlorohexyl)-3-(2,4,5-trimethylphenyl)urea

1-[(4-Butylphenyl)methyl]-1-(6-chlorohexyl(3-(4-chloro-2-methylphenyl)urea

1-[(4-Butylphenyl)methyl]-1-(6-hydroxyhexyl)-3-(2,4,6-trichlorophenyl)urea

1-[(4-Butylphenyl)methyl]-1-(6-cyanohexyl)-3-(2,4,6-trichlorophenyl)urea

1-[(4-Butylphenyl)methyl]-1-(6-chlorohexyl)-3-(2,4,6 -trichlorophenyl)urea

b 1-(4-Phenylbenzyl)-1-(3,4-dichlorobenzyl)-3-(2,4-dimethylphenyl)urea

1-(3,4-Dimethylbenzyl)-1-(2-chlorobenzyl)-3-(2,4-dimethylphenyl)urea

1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)benzyl]-3-(4-chloro-2-methylphenyl)urea

1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)benzyl]-3-(4-chloro2-methylphenyl)urea

1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)benzyl]-3-(2,4,6-trichlorophenyl)urea

1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)benzyl]-3-(2,4-difluorophenyl)urea

1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)benzyl]-3-(2,4-difluorophenyl)urea

1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)benzyl]-3-(2,4,6-trichlorophenyl)urea

1-(5,5-Dimethylhexyl)-1-[4-(n-butyl)benzyl]-3-(4-chloro-2-methylphenyl)urea

1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethylpropyl)benzyl]-3-(2,4-difluorophenyl)urea

1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethylpropyl)benzyl]-3-(4-chloro-2-methylphenyl)urea

1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethylpropyl)benzyl]-3-(2,4,6-trichlorophenyl)urea

1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)benzyl]-3-(4-chloro-2,6-dimethylphenyl)urea

1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-3-(4-chloro-2,6-dimethylphenyl)urea

1-(n-Heptyl)-1-[4-(n-butyl)benzyl]-3-(4-chloro-2,6-dimethylphenyl)urea

1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethylpropyl)benzyl]-3-(4-chloro-2,6-dimethylphenyl)urea

1-(n-Heptyl)-1-[4-(n-butyl)benzyl]-3-(4-chloro-2,5-dimethylphenyl)urea

1-(3,3-Dimethylbutyl)-1-(benzyl)-3-(4-chloro-2,5-dimethylphenyl)urea

1 -(n-Heptyl)-1-[4-(2,2-dimethylpropyl)phenylmethyl]-3-(2,4-difluorophenyl)urea

1-(n-Heptyl)-1-[4-(2,2-dimethylpropyl)phenylmethyl]-3-(4-chloro-2,6-dimethylphenyl)urea

1-(n-Heptyl)-1-[4-(2,2-dimethylpropyl)phenylmethyl]-3-(2,4,6-trifluorophenyl)urea

This invention also relates to a method cf treating atherosclerosis in mammals which comprises administering to said mammal an effective amount of a compound as recited above.

This invention also relates to a method of reducing the cholesterol content of the arterial walls of mammals which comprises administering to said mammal an effective amount of a compound as recited above.

This invention also relates to a method of treating hyperlipidemia in mammals which comprises administering to said mammal an effective amount of a compound as recited above.

This invention further relates to a method of inhibiting atherosclerotic lesion development in mammals which comprises administering to said mammal an effective amount of a compound as recited above.

This invention still further relates to pharmaceutical compositions which comprise an effective antiatherosclerotic amount of a compound as recited above in association with a pharmaceutically acceptable carrier.

Finally, this invention relates to processes for preparing compounds as recited above. One process especially useful for the preparation of ureas and thioureas of Formula I involves reacting an arylisocyanate or arylisothiocyanate of Formula III with a secondary amine of Formula IV, wherein X, Y, R₁, and R₂ are as defined above. ##STR5##

A second process for the preparation of ureas and thioureas of Formula I involves reacting a compound of Formula V; wherein E and B are leaving groups, which may be the same or different, selected from the group consisting of halo, (C₁ -C₄)alkoxy, (C₁ -C₄)alkylthio, phenoxy, 4-chlorophenoxy, and 4-nitrophenoxy; with a secondary amine of Formula IV to yield an intermediate of Formula VI and then reacting the intermediate with an arylamine of Formula VII, wherein X, Y, R₁, and R₂ are as defined above. ##STR6##

A third process for the preparation of ureas and thioureas of Formula I involves reacting a compound of Formula V with an arylamine of Formula VII to yield an intermediate of Formula VIII, wherein X, Y, E, and B are as defined above, and then reacting this intermediate with a secondary amine of Formula IV. ##STR7##

DETAILED DESCRIPTION OF THE INVENTION

Many of the novel ureas and thioureas of this invention are prepared by reacting arylisocyanates and arylisothiocyanates with secondary amines. These reactions may be performed in aprotic solvents such as hexane, diethyl ether, toluene, tetrahydrofuran, and the like at temperatures from room temperature or below up to the boiling point of the solvent used. The ureas and thioureas are isolated by filtration or by evaporation of the solvent, and they may be purified by recrystallization, absorption chromatography, or distillation under reduced pressure Examples of this process are the reaction of 2,4-dimethylphenylisocyanate with N-benzyl-N-(n-butyl)amine to yield 1-benzyl-1-(n-butyl)-3-(2,4-dimethylphenyl)urea and the reaction of 6-[[(4-butylphenyl)methyl]amino]-1-hexanol with 2,4-dimethylphenyl isocyanate in hexane at room temperature to yield 1-[(4-butylphenyl)methyl]-3-(2,4-dimethylphenyl)-1-(6-hydroxyhexyl)urea.

Many of the secondary amines required for the synthesis of the ureas and thioureas of this invention are prepared by reductions of the corresponding amides. Reagents used for these reductions included diborane, lithium aluminum hydride, and sodium dihydrobis(2-methoxyethoxy)aluminate. Examples of this reaction are the syntheses of: 6-[[(4-butylphenyl)methyl]amino]-1-hexanol from 4-butyl-N-(6-hydroxyhexyl)benzamide by treatment with 1M borane-tetrahydrofuran complex in tetrahydrofuran; 4-butyl-N-[5-(trimethylsilyl)pentyl]benzenemethanamine from N-[(4-butylphenyl)methyl]-5-(trimethylsilyl)pentanamide by treatment with lithium aluminum hydride in tetrahydrofuran; 3,3-dimethylbutyl-2-thiophenemethanamine from 3,3-dimethylbutyl-2-thiophenecarboxamide by treatment with Vitride® T [sodium dihydrobis(2-methoxyethoxy)aluminate (70% solution in toluene)]; and N-(n-butyl)-2-chlorobenzylamine by diborane reduction of N-(n-butyl)-2-chlorobenzamide.

Certain of the amides required by these reductions are prepared by acylation of primary amines with carboxylic acids by methods well known to those skilled in the art, for example, by conversion of the carboxylic acid to the corresponding carboxylic acid chloride using thionyl chloride and then reacting the acid chloride with the primary amine in the presence of a base. One method especially useful for this transformation is the boron trifluoride etherate catalyzed reaction of a carboxylic acid with a primary amine An example of this transformation is the boron trifluoride etherate catalyzed acylation of 2-chlorobenzylamine with 3-methoxyphenylacetic acid to yield N-(2-chlorobenzyl)-3-methoxyphenylacetamide. Another example of this reaction is the preparation of 4-butyl-N-(6-hydroxyhexyl)benzamide from 6-amino-1-hexanol, triethylamine and p-butylbenzoyl chloride in dichlcromethane.

Certain of the novel ureas and thioureas of this invention are prepared by reacting arylamines with activated derivatives of carbonic acid such as phosgene or thiophosgene to yield an intermediate, for instance, an arylcarbamyl chloride. This intermediate is then reacted with a secondary amine to yield the urea or thiourea. The preparation of this intermediate is conducted in an aprotic solvent such as tetrahydrofuran, toluene, or xylene at temperatures from about room temperature up to the boiling point of the solvent in the presence of a base, for example, N,N-dimethylaniline. The intermediate is then reacted with an arylamine in an aprotic solvent such as dimethylacetamide in the presence of a base such as sodium hydride at temperatures from about room temperature up to the boiling point of the solvent used.

Other of the novel ureas and thioureas of this invention are prepared by reacting arylamines with activated derivatives of carbonic acid such as phosgene or thiophosgene to yield an intermediate, for instance, an arylcarbamyl chloride. This intermediate is then reacted with a secondary amine to yield the urea or thiourea. The preparation of this intermediate is conducted in an aprotic solvent such as toluene or xylene at temperatures from about room temperature up to the boiling point of the solvent in the presence of a base, for example, N,N-dimethylaniline.

The intermediate is then reacted with a secondary amine in an aprotic solvent such as toluene at temperatures from room temperature or below up to the boiling point of the solvent. An example of this process is the reaction of 2,4-difluoroaniline with phenyl chloroformate to yield the intermediate phenyl N-(2,4-difluorophenyl)carbamate which is then reacted with N-(4-butylphenyl)-N-(6-hydroxyhexyl)amine to yield 1-(4-n-butylphenyl)-3-(2,4-difluorophenyl)-1-(6-hydroxyhexyl)urea.

The ureas and thioureas of this invention which contain carboxy groups are prepared by alkaline hydrolysis of the corresponding carboalkoxy ureas and thioureas, prepared by the synthetic methods described above. Likewise, those which contain hydroxy, mercapto, or amino groups are prepared by alkaline hydrolysis of the corresponding O-acetyl, S-acetyl, and N-acetyl ureas and thioureas, respectively, the latter also having been obtained by the urea and thiourea syntheses described above. Alternatively, ureas and thioureas containing hydroxy groups are prepared by cleavage of the corresponding methoxy compounds using Lewis acids such as boron tribromide.

One of the intermediates, 5-(trimethylsilyl)pentanoic acid, was prepared by reaction of the Grignard reagent derived from bromomethyltrimethylsilane with the magnesium salt of 4-bromobutyric acid.

The ureas and thioureas of the present invention, in general, are obtained as crystalline solids or distillable liquids. They are characterized by distinct melting and boiling points and unique spectra. They are appreciably soluble in organic solvents but generally less soluble in water. Those compounds which contain carboxylic acid groups may be converted to their alkali metal and alkaline earth salts by treatment with the appropriate metal hydroxides, and those which contain amino groups may be converted to their ammonium salts by treatment with organic or mineral acids. Both of these types of salts exhibit increased water solubility.

The preparation and properties of the compounds of this invention will be described in greater detail in conjunction with the specific examples shown below.

The compounds of the present invention were assayed for two types of biological activity related to their potential use as antiatherosclerotic agents. Compounds were tested in vitro for the ability to inhibit the enzyme fatty acyl CoA:cholesterol acyl transferase (ACAT) and in vivo for serum hypolipidemic activity as meausred by the ability to inhibit lipid absorption in rats.

The compounds were tested for their ability to inhibit ACAT according to the following procedure: rat adrenals were homogenized in 0.2M monobasic potassium phosphate buffer, pH 7.4, and centrifuged at 1,000 times gravity for 15 minutes at 5° C. The supernatant, containing the microsomal fraction, served as the source of the cholesterol-esterifying enzyme, fatty acyl CoA:cholesterol acyl transferase (ACAT) A mixture comprising 50 parts of adrenal supernatant, 10 parts of bovine serum albumin (50 mg/ml), 3 parts of test compound (final concentration 5.2 μg/ml), and 500 parts of buffer was preincubated at 37° C. for 10 minutes. After treatment with 20 parts of oleoyl CoA (¹⁴ C-0.4 μCi), the mixture was incubated at 37° C. for 10 minutes. A control mixture, omitting the test compound, was prepared and treated in the same manner. The lipids from the incubation mixture were extracted into an organic solvent and separated by thin-layer chromatography. The cholesteryl ester fraction was counted in a scintillation counter. This procedure is a modification of that described by Hashimoto, et ,la , Life Scie., 12 (Part II), 1-12 (1973).

Compounds which produced statistically significant inhibition of the ACAT enzyme are considered to be active. The results of this test on representative: compounds of this invention appear in Table I.

                  TABLE 1                                                          ______________________________________                                         Compound               % Inhibition                                            ______________________________________                                         1-Benzyl-1-( -n-butyl)-3-(3-methylphenyl)-                                                            92.3                                                    urea                                                                           1-Benzyl-1-( -n-butyl)-3-(3-trifluoromethyl-                                                          85.7                                                    phenyl)urea                                                                    1-Benzyl-1-( -n-butyl)-3-(3,5-dichlorophen-                                                           90.7                                                    yl)urea                                                                        1-Benzyl-1-( -n-butyl)-3-(3,4-dichlorophen-                                                           95.9                                                    yl)urea                                                                        1-Benzyl-1-( -n-butyl)-3-(3-chlorophenyl)-                                                            88.6                                                    urea                                                                           1-Benzyl-1-( -n-butyl)-3-(2,4-dimethylphen-                                                           91.3                                                    yl)urea                                                                        1-Benzyl-1-( -n-butyl)-3-(2-methylphenyl)-                                                            78.8                                                    urea                                                                           1-Benzyl-1-( -n-butyl)-3-(4-methylphenyl)-                                                            78.0                                                    urea                                                                           1-Benzyl-1-( -n-butyl)-3-(2,3-dimethylphen-                                                           85.8                                                    yl)urea                                                                        1-Benzyl-1-( -n-butyl)-3-(2,5-dimethylphen-                                                           92.7                                                    yl)urea                                                                        1-Benzyl-1-( -n-butyl)-3-(2,6-dimethylphen-                                                           83.1                                                    yl)urea                                                                        1-Benzyl-1-( -n-butyl)-3-(3,5-dimethylphen-                                                           94.2                                                    yl)urea                                                                        1-Benzyl-1-[1-(3-methoxyphenyl)-2-phenyl-                                                             86.4                                                    ethyl]-3-(2,4-dimethylphenyl)urea                                              1-Benzyl-1-[1-(4-benzyloxyphenyl)-2-phen-                                                             93.0                                                    ylethyl]-3-(2,4-dimethylphenyl)urea                                            1-Benzyl-1-(1,2-diphenylethyl)-3-(2,4-di-                                                             95.0                                                    methylphenyl)urea                                                              1-Benzyl-1-( -n-butyl)-3-(3,4-dimethylphenyl-                                                         87.1                                                    yl)urea                                                                        1-Benzyl-1-[1-(3-methoxyphenyl)-2-phenyl-                                                             88.1                                                    ethyl]-3-(3-trifluoromethylphenyl)urea                                         1-Benzyl-1-( -n-butyl)-3-(3-chloro-2-methoxy-                                                         84.5                                                    phenyl)urea                                                                    1-Benzyl-1-( -n-butyl)-3-(5-chloro-2-methoxy-                                                         80.6                                                    phenyl)urea                                                                    1-Benzyl-1-(n-butyl)-3-phenyl thiourea                                                                82.4                                                    1-(n-Butyl)-1-(2-fluorobenzyl)-3-(2,4-di-                                                             83.6                                                    methylphenyl)urea                                                              1-(n-Butyl)-1-(4-fluorobenzyl)-3-(2,4-di-                                                             80.6                                                    methylphenyl)urea                                                              1-(n-Butyl)-1-(2-chlorobenzyl)-3-(2,4-di-                                                             95.5                                                    methylphenyl)urea                                                              1-(n-Butyl)-1-(2,6-dichlorobenzyl)-3-(2,4-                                                            74.5                                                    dimethylphenyl)urea                                                            1-(n-Butyl)-1-(4-bromobenzyl)-3-(2,4-di-                                                              81.0                                                    methylphenyl)urea                                                              1-(n-Butyl)-1-[4-(n-butyl)benzyl)-3-(2,4-                                                             94.4                                                    dimethylphenyl)urea                                                            1-(n-Butyl)-1-(4-methylbenzyl)-3-(2,4-di-                                                             96.7                                                    methylphenyl)urea                                                              1-(n-Butyl)-1-(4-tert-butylbenzyl)-3-(2,4                                                             96.4                                                    dimethylphenyl)urea                                                            1-(n-Butyl)-1-(4-chlorobenzyl)-3-(2,4-di-                                                             94.6                                                    methylphenyl)urea                                                              1-(n-Butyl)-1-(4-methoxybenzyl)-3-(2,4-di-                                                            94.2                                                    methylphenyl)urea                                                              1-(n-Butyl)-1-(4-methylenedioxybenzyl)-3-                                                             88.2                                                    (2,4-dimethylphenyl)urea                                                       1-(n-Butyl)-1-(4-trifluoromethylbenzyl)-3-                                                            93.3                                                    (2,4-dimethylphenyl)urea                                                       1-(n-Butyl)-1-(4-phenylbenzyl)-3-(2,4-di-                                                             97.1                                                    methylphenyl)urea                                                              1-(n-Decyl)-1-benzyl-3-(2,4-dimethyl-                                                                 96.1                                                    phenyl)urea                                                                    1-(n-Butyl)-1-(2-phenylethyl)-3-(2,4-di-                                                              87.9                                                    methylphenyl)urea                                                              1-(n-Butyl)-1-[2-(4-fluorophenyl)ethyl]-                                                              96.1                                                    3-(2,4-dimethylphenyl)urea                                                     1-(n-Butyl)-1-[2-(4-chlorophenyl)ethyl]-                                                              93.3                                                    3-(2,4-dimethylphenyl)urea                                                     1-(n-Butyl)-1-[2-(3-methoxyphenyl)ethyl]-                                                             98.3                                                    3-(2,4-dimethylphenyl)urea                                                     1-(n-Butyl)-1-(3-phenylpropyl)-3-(2,4-di-                                                             97.4                                                    methylphenyl)urea                                                              1-(n-Butyl)-1-benzyl-3-(2,4,6-trimethyl-                                                              75.8                                                    phenyl)urea                                                                    1-(n-Butyl)-1-[4-(n-hexyl)benzyl]-3-(2,4-                                                             93.8                                                    dimethylphenyl)urea                                                            1-(n-Tetradecyl)-1-benzyl-3-(2,4-dimethyl-                                                            80.3                                                    phenyl)urea                                                                    1-(n-Butyl)-1-[2-(3-bromophenyl)ethyl]-3-                                                             97.0                                                    (2,4-dimethylphenyl)urea                                                       1-[2-(3,4-Dimethoxyphenyl)ethyl]-1-                                                                   53.3                                                    (3-chloro-4-methylbenzyl)-3-(2,4-                                              dimethylphenyl)urea                                                            1-[2-(2-Methylphenyl)ethyl]-1-(4-bromo-                                                               29.2                                                    benzyl)-3-(2,4-dimethylphenyl)urea                                             1-[2-(3-Trifluoromethylphenyl)ethyl]-1-                                                               7.8                                                     (2-chlorobenzyl)-3-(2,4-dimethylphenyl)                                        urea                                                                           1-(2-Fluorobenzyl)-1-(2-methoxybenzyl)-                                                               41.5                                                    3-(2,4-dimethylphenyl)urea                                                     1-[2-(3,4-Dimethoxyphenyl)ethyl]-1-                                                                   57.4                                                    (4-fluorobenzyl)-3-(2,4-dimethyl-                                              phenyl)urea                                                                    1-[2-(4-Ethoxyphenyl)ethyl]-1-(2,4-di-                                                                34.9                                                    methylbenzyl)-3-(2,4-dimethylphenyl)urea                                       1-[2-(3-Methylphenyl)ethyl]-1-(3-nitro-                                                               95.7                                                    benzyl)-3-(2,4-dimethylphenyl)urea                                             1-[2-(2,5-Dimethoxyphenyl)ethyl]  -1-(3-                                                              97.1                                                    chlorobenzyl)-3-(2,4-dimethylphenyl)urea                                       1-(n-Butyl)-1-(2-methyl-2,2-diphenyl)                                                                 97.4                                                    ethyl-3-(2,4-dimethylphenyl)urea                                               1-(n-Butyl)-1-(4-hexyloxybenzyl)-3-                                                                   97.1                                                    (2,4,6-trimethylphenyl)urea                                                    1-(n-Butyl)-1-(4-heptyloxybenzyl)-3-                                                                  97.3                                                    (2,4,6-trimethylphenyl)urea                                                    1-(n-Butyl)-1-benzyl-3-(4-trifluoro-                                                                  87.8                                                    acetylamino-3,5-dichlorophenyl)urea                                            1-Benzyl-1-(4-n-butylbenzyl)-3-(2,4-                                                                  91.9                                                    dimethylphenyl)urea                                                            1-Benzyl-1-(4-n-butylbenzyl)-3-(2,4,6-                                                                92.8                                                    trimethylphenyl)urea                                                           1-Benzyl-1-(4-n-butylbenzyl)-3-(4-n-                                                                  92.0                                                    butylbenzyl)urea                                                               1-Benzyl-1-(4-n-butylbenzyl)-3-(4-                                                                    93.5                                                    phenoxyphenyl)urea                                                             1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-                                                                   94.8                                                    (2,4-dimethylphenyl)urea                                                       1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-                                                                   95.3                                                    (2,4,5-trimethylphenyl)urea                                                    1-Benzyl-1-[2-phenyl-1-(4-benzyloxy-                                                                  93.7                                                    phenyl)ethyl]-3-(2,4,5-trimethylphenyl)                                        urea                                                                           1-(n-Heptyl)-1-(4-butyloxybenzyl)-3-                                                                  94.6                                                    (2,4-dimethylphenyl)urea                                                       1-(n-Heptyl)-1-(4-butyloxybenzyl)-3-                                                                  95.6                                                    (2,4,5-trimethylphenyl)urea                                                    1-Benzyl-1-(4-butyloxybenzyl)-3-(2,4-                                                                 91.7                                                    dimethylphenyl)urea                                                            1-Benzyl-1-(4-butyloxybenzyl)-3-(2,4,5-                                                               95.8                                                    trimethylphenyl)urea                                                           1-Benzyl-1-(4-n-butylbenzyl)-3-(2,4,5-                                                                90.5                                                    trimethylphenyl)urea                                                           1-Benzyl-1[2-phenyl-1-(4-benzyloxyphenyl                                                              90.0                                                    ethyl]-3-(2,4,6-trimethylphenyl)urea                                           1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-                                                                  90.0                                                    (2,4,6-trichlorophenyl)urea                                                    1-(n-Heptyl)-(4-n-butoxybenzyl)-3-(2,4-                                                               79.9                                                    dichlorophenyl)urea                                                            1-(n-Heptyl)-(4-n-butoxybenzyl)-3-(2-                                                                 89.4                                                    trifluoromethyl-4-chlorophenyl)urea                                            1-Benzyl-1-(4-n-butoxybenzyl)-3-(2,4,6-                                                               95.2                                                    trichlorophenyl)urea                                                           1-Benzyl-1-(4-n-butoxybenzyl)-3-(2,4-                                                                 80.0                                                    dichlorophenyl)urea                                                            1-Benzyl-1-(4-n-butoxybenzyl)-3-(2-                                                                   85.0                                                    trifluoromethyl-4-chlorophenyl)urea                                            1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-(3-                                                               82.4                                                    trifluoromethylphenyl)urea                                                     1-(n-Benzyl-1-(4-n-butoxybenzyl)-3-(3-                                                                87.0                                                    trifluoromethylphenyl)urea                                                     1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4-                                                              80.0                                                    dichlorophenyl)urea                                                            1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2-                                                                90.0                                                    trifluoromethyl-4-chlorophenyl)urea                                            1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-                                                                   90.0                                                    (2,4,6-trichlorophenyl)urea                                                    1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-                                                                   85.0                                                    (3-trifluoromethylphenyl)urea                                                  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-                                                                   46.5                                                    (2,4,5-trichlorophenyl)urea                                                    1-Benzyl-1-(4-n-butylbenzyl)-3-(2-                                                                    94.3                                                    methyl-4-chlorophenyl)urea                                                     1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-                                                                  82.7                                                    (2,4-difluorophenyl)urea                                                       1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-(2-                                                               91.7                                                    methyl-4-chlorophenyl)urea                                                     1-(n-Heptyl)-1-(2-furyl)-3-(2,4,5-tri-                                                                93.8                                                    methylphenyl)urea                                                              1-(n-Heptyl)-1-(2-furyl)-3-(2,4,6-tri-                                                                96.1                                                    chlorophenyl)urea                                                              1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2-                                                                92.5                                                    methyl-4-chlorophenyl)urea                                                     1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4-                                                              90.0                                                    difluorophenyl)urea                                                            1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(4-                                                                92.4                                                    carboethoxyphenyl)urea                                                         1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2-                                                                97.4                                                    methylphenyl)urea                                                              1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(3-                                                                93.8                                                    methylphenyl)urea                                                              1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(4-                                                                61.8                                                    carboxyphenyl)urea                                                             1-(n-Heptyl)-1-(2-phenylethyl)-3-(2-                                                                  93.8                                                    methyl-4-chlorophenyl)urea                                                     1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4,5-                                                              77.3                                                    trichlorophenyl)urea                                                           1-(n-Heptyl)-1-(2-phenylethyl)-3-(2-                                                                  88.3                                                    trifluoromethyl-4-chlorophenyl)urea                                            1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4-                                                                95.7                                                    dimethylphenyl)urea                                                            1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4-                                                                91.8                                                    dichlorophenyl)urea                                                            1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4-                                                                94.1                                                    difluorophenyl)urea                                                            1-(n-Heptyl)-1-(2-phenylethyl)-3-(3-                                                                  88.4                                                    trifluoromethylphenyl)urea                                                     1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphen-                                                              95.0                                                    yl)ethyl]-3-(2,4,6-trichlorophenyl)urea                                        1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxy-                                                                95.5                                                    benzyl)-3-(2,4,6-trichlorophenyl)urea                                          1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxy-                                                                85.0                                                    benzyl)-3-(2,4-dichlorophenyl)urea                                             1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxy-                                                                80.0                                                    benzyl)-3-(2,4,5-trichlorophenyl)urea                                          1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxy-                                                                81.0                                                    benzyl)-3-(2-trifluoromethyl-4-chloro-                                         phenyl)urea                                                                    1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxy-                                                                85.0                                                    benzyl)-3-(3-trifluoromethylphenyl)urea                                        1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxy-                                                                90.0                                                    benzyl)-3-(2,4-difluorophenyl)urea                                             1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxy-                                                                91.0                                                    benzyl)-3-(2-methyl-4-chlorophenyl)urea                                        1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-                                                              77.0                                                    3-(2,4,6-trichlorophenyl)urea                                                  1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-                                                              94.0                                                    3-(2-methyl-4-chlorophenyl)urea                                                1-(4-Chlorophenyl)-1-(1-naphthylmethyl)-                                                              84.0                                                    3-(2,4-difluorophenyl)urea                                                     1-(4-Chlorophenyl)-1-(1-naphthylmethyl)-                                                              80.0                                                    3-(3-trifluoromethylphenyl)urea                                                1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-                                                              86.0                                                    3-(2,4,5-trichlorophenyl)urea                                                  1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphen-                                                              95.0                                                    yl)ethyl]-3-(2,4,5-trichlorophenyl)urea                                        1-Benzyl-1-(4-n-butyloxybenzyl)-3-(2,4,5-                                                             89.0                                                    trichlorophenyl)urea                                                           1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphen-                                                              70.0                                                    yl)ethyl]-3-(2,4-difluorophenyl)urea                                           1-Benzyl-1-(4-n-butoxybenzyl)-3-(2,4-                                                                 88.0                                                    difluorophenyl)urea                                                            1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphe-                                                               91.0                                                    nyl)ethyl]-3-(2,4-difluorophenyl)urea                                          1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphe-                                                               92.0                                                    nyl)ethyl]-3-(2-trifluoromethyl-4-                                             chlorophenyl)urea                                                              1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphe-                                                               74.0                                                    nyl)ethyl]-3-(3-trifluoromethylphenyl)                                         urea                                                                           1-[(4-Butylphenyl)methyl]-3-(2,4-dimethyl-                                                            96.8                                                    phenyl)-1-(6-hydroxyhexyl)urea                                                 1-[(4-Butylphenyl)methyl]-1-(6-hydroxy-                                                               90.0                                                    hexyl)-3-(2,4,5-trimethylphenyl)urea                                           1-[(4-Butylphenyl)methyl]-1-[2-(2-hydroxy-                                                            85.9                                                    ethoxy)ethyl]-3-(2,4,5-trimethylphenyl)urea                                    1-[(4-Butylphenyl)methyl]-3-(2,4-dimethyl-                                                            74.5                                                    phenyl)-1-[2-(2-hydroxyethoxy)ethyl]urea                                       1-(2-Furanylmethyl)-1-heptyl-3-(2,4,5-                                                                93.8                                                    trimethylphenyl)urea                                                           1-(2-Furanylmethyl)-1-heptyl-3-(2,4,6-                                                                96.1                                                    trichlorophenyl)urea                                                           1-Heptyl-1-(2-thienylmethyl)-3-(2,4,5-                                                                90.0                                                    trimethylphenyl)urea                                                           1-Heptyl-1-(2-thienylmethyl)-3-(2,4,6-                                                                90.0                                                    trichlorophenyl)urea                                                           1-[(4-Butoxyphenyl)methyl]  -1-(2-thienyl-                                                            90.0                                                    methyl)-3-(2,4,5-trimethylphenyl)urea                                          1-[(4-Butylphenyl)methyl]-1-[6-[(methyl-                                                              90.0                                                    sulfonyl)oxy]hexyl]-3-[(2,4,5-trimethyl-                                       phenyl)methyl]urea                                                             1-[(4-Butylphenyl)methyl]-1-(6-cyanohexyl)-                                                           90.0                                                    3-(2,4,5-trimethylphenyl)urea                                                  1-[(4-Butylphenyl)methyl]-1-(6-chlorohex-                                                             90.0                                                    yl)-3-(2,4,5-trimethylphenyl)urea                                              1-[(4-Butylphenyl)methyl]-3-(4-chloro-2-                                                              90.0                                                    methylphenyl)-1-(6-hydroxyhexyl)urea                                           1-[(4-Butylphenyl)methyl]-3-(4-chloro-2-                                                              90.0                                                    methylphenyl)-1-[6-[(methylsulfonyl)oxy]-                                      hexyl]urea                                                                     1-[(4-Butylphenyl)methyl]-3-(4-chloro-2-                                                              90.0                                                    methylphenyl)-1-(6-cyanohexyl)urea                                             1-[(4-Butylphenyl)methyl]-1-(6-chlorohex-                                                             90.0                                                    yl)-3-(4-chloro-2-methylphenyl)urea                                            1-[(4-Butylphenyl)methyl]-1-(6-hydroxy-                                                               90.0                                                    hexyl)-3-(2,4,6-trichlorophenyl)urea                                           1-[(4-Butylphenyl)methyl]-1-(6-[(methyl-                                                              90.0                                                    sulfonyloxy)hexyl]-3-(2,4,6-trichloro-                                         phenyl)urea                                                                    1-[(4-Butylphenyl)methyl]-1-(6-cyanohex-                                                              90.0                                                    yl)-3-(2,4,6-trichlorophenyl)urea                                              1-[(4-Butylphenyl)methyl]-1-(6-chlorohex-                                                             90.0                                                    yl)-3-(2,4,6-trichlorophenyl)urea                                              1-[(4-Butylphenyl)methyl]-3-(4-chloro-2-                                                              90.0                                                    methylphenyl)-1-[5-(trimethylsilyl)pentyl]-                                    urea                                                                           1-[(4-Butylphenyl)methyl]-3-(2,4-difluoro-                                                            90.0                                                    phenyl)-1-[5-(trimethylsilyl)pentyl]urea                                       3-(2,4-Difluorophenyl)-1-(3,3-dimethyl-                                                               90.0                                                    butyl)-1-(2-thienylmethyl)urea                                                 3-(4-Chloro-2-methylphenyl)-1-(3,3-di-                                                                90.0                                                    methylbutyl)-1-(2-thienylmethyl)urea                                           1-(3,3-Dimethylbutyl)-1-(2-thienylmethyl)-                                                            90.0                                                    3-(2,4,6-trichlorophenyl)urea                                                  1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphe-                                                               89.3                                                    nyl)ethyl]-3-(2-methyl-4-chlorophenyl)                                         urea                                                                           1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-                                                              92.0                                                    3-(2,4-dichlorophenyl)urea                                                     1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-                                                              83.0                                                    3-(2-trifluoromethyl-4-chlorophenyl)urea                                       1-[2-(4-Methylphenyl)ethyl]-1-(3-chloro-                                                              67.6                                                    benzyl)-3-(2,4-dimethylphenyl)urea                                             1-[2-(4-Ethoxyphenyl)ethyl]-1-(2-chloro-                                                              94.1                                                    benzyl)-3-(2,4-dimethylphenyl)urea                                             1-(4-Phenylbenzyl)-1-(3,4-dichlorobenzyl)-                                                            36.3                                                    3-(2,4-dimethylphenyl)urea                                                     1-(n-Butyl)-1-benzyl-3-(3-chloro-2-hydroxy-                                                           71.0                                                    phenyl)urea                                                                    1-[2-(3-Fluorophenyl)ethyl]-1-(4-methyl-                                                              80.5                                                    benzyl)-3-(2,4-dimethylphenyl)urea                                             1-(n-Butyl)-1-benzyl-3-(2-nitrophenyl)-                                                               37.0                                                    urea                                                                           1-(3,4-Methylenedioxyphenyl)-1-(3,3-di-                                                               87.8                                                    phenylpropyl)-3-(2,4-dimethylphenyl)urea                                       1-(n-Butyl)-1-[3-(3,4-dimethoxyphenyl)-                                                               36.4                                                    propyl]-3-(2,4-dimethylphenyl)urea                                             1-(3,4-Dimethylbenzyl)-1-(2-chlorobenzyl)-                                                            92.9                                                    3-(2,4-dimethylphenyl)urea                                                     1-(n-Butyl)-1-benzyl-3-(2,4,6-trichloro-                                                              87.8                                                    phenyl)urea                                                                    1-(n-Butyl)-1-benzyl-3-(2-hydroxy-5-                                                                  85.6                                                    chlorophenyl)urea                                                              1-(3,4-Methylenedioxybenzyl)-1-[2-(4-                                                                 41.2                                                    methylphenyl)ethyl]-3-(2,4-dimethyl-                                           phenyl)urea                                                                    1-(n-Butyl)-1-benzyl-3-(4-amino-3,5-                                                                  61.1                                                    dichlorophenyl)urea                                                            1-(n-Butyl)-1-(benzyl)-3-[4-(chloroacet-                                                              72.9                                                    amido)-3,5-dichlorophenyl]urea                                                 1-[2-(2-Chlorophenyl)ethyl]-1-(3,4-di-                                                                92.8                                                    methylbenzyl)-3-(2,4-dimethylphenyl)urea                                       1-[2-(2-Chlorophenyl)ethyl]-1-(3-methyl-                                                              56.1                                                    benzyl)-3-(2,4-dimethylphenyl)urea                                             1-(n-Butyl)-1-benzyl-3-(4-chloro-2-                                                                   89.0                                                    methylphenyl)urea                                                              1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)-                                                                 90.5                                                    benzyl]-3-(4-chloro-2-methylphenyl)urea                                        1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)-                                                                90.0                                                    benzyl[-3-(4-chloro-2-methylphenyl)urea                                        1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)-                                                                90.0                                                    benzyl]-3-(2,4,6-trichlorophenyl)urea                                          1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)-                                                                90.0                                                    benzyl]-3-(2,4-difluorophenyl)urea                                             1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)-                                                                 90.0                                                    benzyl]-3-(2,4-difluorophenyl)urea                                             1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)-                                                                 90.0                                                    benzyl]-3-(2,4,6-trichlorophenyl)urea                                          1-(5,5-Dimethylhexyl)-1-[4-(n-butyl)ben-                                                              90.0                                                    zyl]-3-(4-chloro-2-methylphenyl)urea                                           1-(5,5-Dimethylhexyl)-1-[4-(n-butyl)ben-                                                              90.0                                                    zyl]-3-(2,4-difluorophenyl)urea                                                1-(5,5-Dimethylhexyl)-1-[4-(n-butyl)ben-                                                              90.0                                                    zyl]-3-(2,4,6-trichlorophenyl)urea                                             1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-                                                             90.0                                                    3-(4-chloro-2-methylphenyl)urea                                                1-(3,3-Dimethylbutyl)-1-benzyl-3-(2,4-                                                                90.0                                                    difluorophenyl)urea                                                            1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-                                                             90.0                                                    3-(2,4-difluorophenyl)urea                                                     1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-                                                             90.0                                                    3-(2,4,6-trichlorophenyl)urea                                                  1-(n-Heptyl)-1-[4-(n-butyl)benzyl]-3-(3-                                                              90.0                                                    trifluoromethylphenyl)urea                                                     1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)ben-                                                              90.0                                                    zyl]-3-(3-trifluoromethylphenyl)urea                                           1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-                                                             90.0                                                    3-(3-trifluoromethylphenyl)urea                                                1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethyl-                                                             90.0                                                    propyl)benzyl]-3-(2,4-difluorophenyl)urea                                      1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethyl-                                                             90.0                                                    propyl)benzyl]-3-(4-chloro-2-methylphenyl)                                     urea                                                                           1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethyl-                                                             90.0                                                    propyl)benzyl]-3-(2,4,6-trichlorophenyl)                                       urea                                                                           1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)ben-                                                              90.0                                                    zyl]-3-(4-chloro-2,6-dimethylphenyl)urea                                       1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-                                                             90.0                                                    3-(4-chloro-2,6-dimethylphenyl)urea                                            1-(n-Heptyl)-1-[4-(n-butyl)benzyl]-3-(4-                                                              90.0                                                    chloro-2,6-dimethylphenyl)urea                                                 1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethyl-                                                             90.0                                                    propyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                       phenyl)urea                                                                    1-(3,3-Dimethylbutyl)-1-benzyl-3-(4-                                                                  90.0                                                    chloro-2-methylphenyl)urea                                                     1-(n-Heptyl)-1-[4-(n-butyl)benzyl]-3-(4-                                                              90.0                                                    chloro-2,5-dimethylphenyl)urea                                                 1-(3,3-Dimethylbutyl)-1-(benzyl)-3-(4-                                                                90.0                                                    chloro-2,5-dimethylphenyl)urea                                                 1-( -n-Heptyl)-1-[4-( -n-butyl)benzyl]-3-                                                             90.0                                                    (2,4,6-trifluorophenyl)urea                                                    1-(3,3-Dimethylbutyl)-1-[4-( -n-butyl)ben-                                                            90.0                                                    zyl]-3-(2,4,6-trifluorophenyl)urea                                             1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethyl-                                                             90.0                                                    propyl)benzyl]-3-(2,4,6-trifluorophenyl)urea                                   1-(3,3-Dimethylbutyl)-1-benzyl-3-(2,4,6-                                                              90.0                                                    trifluorophenyl)urea                                                           ______________________________________                                    

In addition to the above described test and the results given in terms of percent inhibition, various compounds of this invention were tested by the same procedure at several concentrations. The results of this test are given in Table II inn terms of IC₅₀ (μM), that concentration which produced 50% inhibition of the ACAT enzyme.

                  TABLE II                                                         ______________________________________                                         Compound                  IC.sub.50 (μM)                                    ______________________________________                                         1-(6-Hydroxyheptyl)-1-[4-(2,2-dimethylpropyl)-                                                           1.13                                                 benzyl]-3-(4-chloro-2,6-dimethylphenyl)urea                                    1-(Isopentyl)-1-[4-(isopropyl)benzyl]-3-(2,4-                                                            3.37                                                 difluorophenyl)urea                                                            1-(Isopentyl)-1-[4-(isopropyl)benzyl]-3-(4-                                                              0.54                                                 chloro-2,6-dimethylphenyl)urea                                                 1-(Isopentyl)-1-[4-(isopropyl)benzyl]-3-(2,4,6-                                                          0.53                                                 trifluorophenyl)urea                                                           1-(n-Heptyl)-1-[4-(isobutyl)benzyl]-3-(4-                                                                1.84                                                 chloro-2-methylphenyl)urea                                                     1-(n-Heptyl)-1-[4-(isopropyl)benzyl]-3-(2,4-                                                             1.17                                                 difluorophenyl)urea                                                            1-(n-Heptyl)-1-[4-(isopropyl)benzyl]-3-(4-                                                               0.20                                                 chloro-2,6-dimethylphenyl)urea                                                 1-(n-Heptyl)-1-[4-(isopropyl)benzyl]-3-(4-                                                               1.74                                                 chloro-2-methylphenyl)urea                                                     1-(n-Heptyl)-1-[4-(isopropyl)benzyl]-3-(2,4,6-                                                           0.35                                                 trifluorophenyl)urea                                                           1-(n-Heptyl)-1-[4-(4-isopentyl)benzyl]-3-(4-                                                             2.40                                                 chloro-2-methylphenyl)urea                                                     1-(n-Heptyl)-1-[4-(isopentyl)benzyl]-3-(4-                                                               0.13                                                 chloro-2,6-dimethylphenyl)urea                                                 1-(n-Heptyl)-1-[4-(4-hydroxybutyl)benzyl]-3-                                                             0.82                                                 (4-chloro-2,6-dimethylphenyl)urea                                              1-(n-Heptyl)-1-[4-(3-carboxypropyl,)benzyl]-3-                                                           7.22                                                 (4-chloro-2,6-dimethylphenyl)urea                                              1-(n-Heptyl)-1-[4-(4-chlorobutyl)benzyl]-3-                                                              0.11                                                 (4-chloro-2,6-dimethylphenyl)urea                                              1-(n-Heptyl)-1-[4-(3-carboethoxypropyl)benzyl]-                                                          108                                                  3-(4-chloro-2,6-dimethylphenyl)urea                                            ______________________________________                                    

The compounds of this invention were tested in vitro at several concentrations for their ability to inhibit the enzyme fatty acyl CoA:cholesterol acyl transferase (ACAT) using the hereinabove described procedure except that the enzyme was derived from microsomes isolated from rat intestinal mucosal cells rather than rat adrenal cells. The results of this test on representative compounds of this invention are given in Table III in terms of IC₅₀ (μM), that concentration which produced 50% inhibition of the ACAT enzyme.

                  TABLE III                                                        ______________________________________                                         Compound                  IC.sub.50 (μM)                                    ______________________________________                                         1-(n-Heptyl)-1-[4-(carbomethoxymethyl)benzyl]-                                                           1.75                                                 3-(2,4-difluorophenyl)urea                                                     1-(n-Heptyl)-1-[4-(carboxymethyl)benzyl]-3-                                                              24.0                                                 (2,4-difluorophenyl)urea                                                       1-(n-Heptyl)-1-[4-(3-carboxypropyl)benzyl]-3-                                                            1.02                                                 (4-chloro-2,6-dimethylphenyl)urea                                              1-(n-Heptyl)-1-[4-(4-isopropylthiobutyl)ben-                                                             3.27                                                 zyl]-3-(2,4-difluorophenyl)urea                                                1-(n-Heptyl)-1-[4-(cyclopentylmethyl)benzyl]-3-                                                          0.14                                                 (2,4-difluorophenyl)urea                                                       1-(n-Heptyl)-1-[4-(hydroxymethyl)benzyl]-3-                                                              0.20                                                 (2,4-difluorophenyl)urea                                                       1-(n-Heptyl)-1-[4-(acetoxymethyl)benzyl]-3-                                                              0.12                                                 (2,4-difluorophenyl)urea                                                       1-(n-Heptyl)-1-[4-(2-isopropylthioethyl)ben-                                                             0.21                                                 zyl]-3-(2,4-difluorophenyl)urea                                                1-(n-Heptyl)-1-[4-(2,3-dimethylpentyl)benzyl]-                                                           0.02                                                 3-(4-chloro-2,6-dimethylphenyl)urea                                            1-(n-Heptyl)-1-[4-(2-isopropylsulfinylethyl)-                                                            0.22                                                 benzyl]-3-(2,4-difluorophenyl)urea                                             1-(n-Heptyl)-1-[4-(isopentyloxymethyl)benzyl]-                                                           0.33                                                 3-(2,4-difluorophenyl)urea                                                     1-(n-Heptyl)-1-[4-(isopentyloxymethyl)benzyl]-                                                           0.18                                                 3-(2,4,6-trifluorophenyl)urea                                                  1-(n-Heptyl)-1-[4-(isopentyloxymethyl)benzyl]-                                                           0 13                                                 3-(4-chloro-2,6-dimethylphenyl)urea                                            ______________________________________                                    

Inhibition of cholesterol absorption was determined by feeding male Sprague-Dawley rats, weighing 150-170 g, a 1% cholesterol:0.5% cholic acid diet for 2 weeks. The diet also contained compounds being tested at a dose of 0.001, 0.003, 0.01, or 0.03% of the diet. Control rats were fed the same diet without any compound At the end of the test, the rats were sacrificed by decapitation. Blood was collected, centrifuged at 1.5 times gravity for 10 minutes at 4° C.; and the serum was then analyzed for cholesterol and triglycerides enzymatically by the method of Trinder, P., Analyst, 77, 321 (1952) on a Centrifichem 400 analyzer Livers were removed, a 0.4 g sample was taken from the center of the large lobe, and the sample was subjected to saponification using 25% saturated potassium hydroxide in ethanol. The resulting neutral sterols were extracted with petroleum ether and the extract analyzed for cholesterol. The effectiveness of the compound in inhibiting cholesterol absorption was measured by the lowering of either serum cholesterol or liver cholesterol relative the values for control rats.

Compounds which produced statistically significant inhibition of cholesterol absorption are considered to be active. Liver sterol (LS) and serum sterol (SS) values are expressed as a percentage of control values. The results of this test on typical compounds of this invention appear in Table IV.

                  TABLE IV                                                         ______________________________________                                         Compound               Dose %   LS    SS                                       ______________________________________                                         1-Benzyl-1-(n-butyl)-3-(2,4-dimethylphen-                                                             .03      65    70                                       yl)urea                                                                        1-Benzyl-1-(n-butyl)-3-(2,6-dimethylphen-                                                             .03      91    68                                       yl)urea                                                                        1-Benzyl-1-(n-butyl)-3-(3,5-dimethylphen-                                                             .03      75    93                                       yl)urea                                                                        1-Benzyl-1-(1,2-diphenylethyl)-3-(2,4-                                                                .03      63    52                                       dimethylphenyl)urea                                                            1-(2-Fluorobenzyl)-1-(2-methoxybenzyl)-3-                                                             .03      20    45                                       (2,4-dimethylphenyl)urea                                                       1-(n-Butyl)-1-(4-hexyloxybenzyl)-3-(2,4-                                                              .03      15    54                                       trimethylphenyl)urea                                                           1-(n-Butyl)-1-(4-heptyloxybenzyl)-3-                                                                  .03      31    66                                       (2,4,6-trimethylphenyl)urea                                                    1-Benzyl-1-(4-n-butylbenzyl)-3-(2,4-                                                                  .03      20    41                                       dimethylphenyl)urea                                                            1-Benzyl-1-(4-n-butylbenzyl)-3-(2,4,6-                                                                .03      13    53                                       trimethylphenyl)urea                                                           1-Benzyl-1-(4-n-butylbenzyl)-3-(4-n-butyl-                                                            .03      61    53                                       phenyl)urea                                                                    1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4-                                                              .03      14    46                                       dimethylphenyl)urea                                                            1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4,5-                                                            .03      10    33                                       trimethylphenyl)urea                                                           1-(n-Heptyl)-1-(4-butyloxybenzyl)-3-(2,4-                                                             .03      22    26                                       dimethylphenyl)urea                                                            1-(n-Heptyl)-1-(4-butyloxybenzyl)-3-                                                                  .03      17    32                                       (2,4,5-trimethylphenyl)urea                                                    1-Benzyl-1-(4-butyloxybenzyl)-3-(2,4-                                                                 .03      15    48                                       dimethylphenyl)urea                                                            1-Benzyl-1-(4-butyloxybenzyl)-3-(2,4,5-                                                               .03      12    43                                       trimethylphenyl)urea                                                           1-Benzyl-1-(4-n-butylbenzyl)-3-(2,4,5-                                                                .03      10    50                                       trimethylphenyl)urea                                                           1-Benzyl-1-[2-phenyl-1-(4-benzyloxy-                                                                  .03      49    60                                       phenyl)ethyl]-3-(2,4,6-trimethylphenyl)-                                       urea                                                                           1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-                                                                  .03      11    35                                       (2,4,6-trichlorophenyl)urea                                                    1-(n-Heptyl)-(4-n-butoxybenzyl)-3-(2,4-                                                               .03      50    68                                       dichlorophenyl)urea                                                            1-(n-Heptyl)-(4-n-butoxybenzyl)-3-(2-tri-                                                             03       35    59                                       fluoromethyl-4-chlorophenyl)urea                                               1-Benzyl-1-(4-n-butoxybenzyl)-3-(2,4,6-                                                               .03       8    40                                       trichlorophenyl)urea                                                           1-Benzyl-1-(4-n-butoxybenzyl)-3-(2,4-                                                                 .03      49    53                                       dichlorophenyl)urea                                                            1-Benzyl-1-(4-n-butoxybenzyl)-3-(2-tri-                                                               .03      31    58                                       fluoromethyl-4-chlorophenyl)urea                                               1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-(3-                                                               .03      86    80                                       trifluoromethylphenyl)urea                                                     1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4-                                                              .03      50    58                                       dichlorophenyl)urea                                                            1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2-                                                                .03      47    63                                       trifluoromethyl-4-chlorophenyl)urea                                            1-(n-Heptyl)-1-(4-butylbenzyl)-3-(2,4,6-                                                              .03       8    28                                       trichlorophenyl)urea                                                           1-Benzyl-1-(4-n-butylbenzyl)-3-(2-methyl-                                                             .03      21    70                                       4-chlorophenyl)urea                                                            1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-(2,4-                                                             .03      25    63                                       difluorophenyl)urea                                                            1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-(2-                                                               .03      15    53                                       methyl-4-chlorophenyl)urea                                                     1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2-                                                                .03      16    35                                       methyl-4-chlorophenyl)urea                                                     1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4-                                                              .03      19    35                                       difluorophenyl)urea                                                            1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(4-                                                                .03      84    88                                       carboethoxyphenyl)urea                                                         1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2-                                                                .03      29    35                                       methylphenyl)urea                                                              1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(3-                                                                .03      42    49                                       methylphenyl)urea                                                              1-(n-Heptyl)-1-(2-phenylethyl)-3-(2-                                                                  .03      49    66                                       methyl-4-chlorophenyl)urea                                                     1-(n-Heptyl)-1-(2-phenylethyl)-3-(2-                                                                  .03      80    79                                       trifluoromethyl-4-chlorophenyl)urea                                            1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4-                                                                .03      36    57                                       dimethylphenyl)urea                                                            1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4-di-                                                             .03      88    81                                       chlorophenyl)urea                                                              1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4-                                                                .03      57    59                                       difluorophenyl)urea                                                            1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphen-                                                              03       64    95                                       yl)ethyl]-3-(2,4,6-trichlorophenyl)urea                                        1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxy-                                                                03       76    100                                      benzyl)-3-(2,4,6-trichlorophenyl)urea                                          1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxy-                                                                .03      92    91                                       benzyl)-3-(2,4-dichlorophenyl)urea                                             1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxy-                                                                .03      92    85                                       benzyl)-3-(2,4,5-trichlorophenyl)urea                                          1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxy-                                                                .03      67    55                                       benzyl)-3-(2,4-difluorophenyl)urea                                             1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-                                                            .03      12    38                                       (2,4,6-trichlorophenyl)urea                                                    1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-                                                              .03      17    35                                       3-(2-methyl-4-chlorophenyl)urea                                                1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-                                                            .03      30    45                                       (2,4-difluorophenyl)urea                                                       1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-                                                            .03      92    87                                       (3-trifluoromethylphenyl)urea                                                  1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-                                                            .03      97    84                                       (2,4,5-trichlorophenyl)urea                                                    1-Benzyl-1-(4-n-butyloxybenzyl)-3-(2,4,5-                                                             .03      65    66                                       trichlorophenyl)urea                                                           1-Benzyl-1-[2-phenyl-1-(4-benzyloxy-                                                                  .03      27    48                                       phenyl)-ethyl]-3-(2,4-difluorophenyl)urea                                      1-Benzyl-1-(4-n-butoxybenzyl)-3-(2,4-di-                                                              .03      22    53                                       fluorophenyl)urea                                                              1-Benzyl-1-[2-phenyl-1-(4-benzyloxy-                                                                  .03      31    50                                       phenyl)ethyl]-3-(2-methyl-4-chlorophenyl)-                                     urea                                                                           1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-                                                              .03      48    50                                       3-(2,4-dichlorophenyl)urea                                                     1-[(4-Butylphenyl)methyl]-1-(6-hydroxy-                                                               03       39    57                                       hexyl)-3-(2,4,5-trimethylphenyl)urea                                           1-[(4-Butylphenyl)methyl]-1-[2-(2-hydroxy-                                                            .03      76    100                                      ethoxy)ethyl]-3-(2,4,5-trimethylphenyl)-                                       urea                                                                           1-(2-Furanylmethyl)-1-heptyl-3-(2,4,5-                                                                .03      38    44                                       trimethylphenyl)urea                                                           1-(2-Furanylmethyl)-1-heptyl-3-(2,4,6-                                                                .03      34    37                                       trichlorophenyl)urea                                                           1-Heptyl-1-(2-thienylmethyl)-3-(2,4,5-                                                                .03      25    54                                       trimethylphenyl)urea                                                           1-Heptyl-1-(2-thienylmethyl)-3-(2,4,6-                                                                .03      28    56                                       trichlorophenyl)urea                                                           1-[(4-Butoxyphenyl)methyl]-1-(2-thienyl-                                                              .03      16    41                                       methyl)-3-(2,4,5-trimethylphenyl)urea                                          1-[(4-Butylphenyl)methyl]-1-(6-cyano-                                                                 .03      28    48                                       hexyl)-3-(2,4,5-trimethylphenyl)urea                                           1-[(4-Butylphenyl)methyl]-1-(6-chloro-                                                                .03      15    40                                       hexyl)-3-(2,4,5-trimethylphenyl)urea                                           1-[(4-Butylphenyl)methyl]-3-(4-chloro-2-                                                              .03      53     6                                       methylphenyl)-1-(6-hydroxyhexyl)urea                                           1-[(4-Butylphenyl)methyl]-3-(4-chloro-2-                                                              .03      50    48                                       methylphenyl)-1-(6-cyanohexyl)urea                                             1-[(4-Butylphenyl)methyl]-1-(6-chloro-                                                                .03      35    46                                       hexyl)-3-(4-chloro-2-methylphenyl)urea                                         1-[(4-Butylphenyl)methyl]-1-(6-hydroxy-                                                               .03      32    35                                       hexyl)-3-(2,4,6-trichlorophenyl)urea                                           1-[(4-Butylphenyl)methyl]-1-(6-cyano-                                                                 .03      35    31                                       hexyl)-3-(2,4,6-trichlorophenyl)urea                                           1-[(4-Butylphenyl)methyl]  -1-(6-chloro-                                                              .03      19    34                                       hexyl)-3-(2,4,6-trichlorophenyl)urea                                           1-[(4-Butylphenyl)methyl]-3-(4-chloro-2-                                                              .03      62    50                                       methylphenyl)-1-[5-(trimethylsilyl)-                                           pentyl]urea                                                                    1-[(4-Butylphenyl)methyl]-3-(2,4-difluoro-                                                            .03      57    62                                       phenyl)-1-[5-(trimethylsilyl)pentyl]urea                                       3-(2,4-Difluorophenyl)-1-(3,3-dimethyl-                                                               .03      73    66                                       butyl)-1-(2-thienylmethyl)urea                                                 3-(4-Chloro-2-methylphenyl)-1-(3,3-di-                                                                .03      64    62                                       methylbutyl)-1-(2-thienylmethyl)urea                                           1-(3,3-Dimethylbutyl)-1-(2-thienylmethyl)-                                                            .03      56    58                                       3-(2,4,6-trichlorophenyl)urea                                                  1-[2-(4-Methylphenyl)ethyl]-1-(3-chloro-                                                              .03      20    50                                       benzyl)-3-(2,4-dimethylphenyl)urea                                             1-(4-Phenylbenzyl)-1-(3,4-dichloro-                                                                   .03      17    49                                       benzyl)-3-(2,4-dimethylphenyl)urea                                             1-(3,4-Dimethylbenzyl)-1-(2-chlorobenzyl)-                                                            .03      15    44                                       3-(2,4-dimethylphenyl)urea                                                     1-(n-Butyl)-1-benzyl-3-(2,4,6-trichloro-                                                              .03      32    48                                       phenyl)urea                                                                    1-(n-Butyl)-1-benzyl-3-(4-chloro-2-methyl-                                                            .03      62    72                                       phenyl)urea                                                                    1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)-                                                                 .03      13    46                                       benzyl]-3-(4-chloro-2-methylphenyl)urea                                        1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)-                                                                .03      22    61                                       benzyl]-3-(4-chloro-2-methylphenyl)urea                                        1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)-                                                                .03      20    52                                       benzyl]-3-(2,4,6-trichlorophenyl)urea                                          1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)-                                                                .03      32    42                                       benzyl]-3-(2,4-difluorophenyl)urea                                             1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)-                                                                 .03      30    39                                       benzyl]-3-(2,4-difluorophenyl)urea                                             1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)-                                                                 .03      13    37                                       benzyl]-3-(2,4,6-trichlorophenyl)urea                                          1-(5,5-Dimethylhexyl)-1-[4-(n-butyl)-                                                                 .03      34    42                                       benzyl]-3-(4-chloro-2-methylphenyl)urea                                        1-(5,5-Dimethylhexyl)-1-[4-(n-butyl)-                                                                 .03      58    59                                       benzyl]-3-(2,4-difluorophenyl)urea                                             1-(5,5-Dimethylhexyl)-1-[4-(n-butyl)-                                                                 .03      32    45                                       benzyl]-3-(2,4,6-trichlorophenyl)urea                                          1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-                                                             .03      60    50                                       3-(4-chloro-2-methylphenyl)urea                                                1-(3,3-Dimethylbutyl)-1-benzyl-3-(2,4-                                                                .03      70    71                                       difluorophenyl)urea                                                            1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-                                                             .03      41    73                                       3-(2,4,6-trichlorophenyl)urea                                                  1-(n-Heptyl)-1-[4-(n-butyl)benzyl]-3-(4-                                                              .03      88    79                                       trifluoromethylphenyl)urea                                                     1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)ben-                                                              .03      86    100                                      zyl]-3-(4-trifluoromethylphenyl)urea                                           1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-                                                             .03      70    85                                       3-(4-trifluoromethylphehyl)urea                                                1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethyl-                                                             .03      19    35                                       propyl)benzyl]-3-(2,4-difluorophenyl)urea                                      1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethyl-                                                             .03      20    51                                       propyl)benzyl]-3-(4-chloro-2-methyl-                                           phenyl)urea                                                                    1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethyl-                                                             .03      15    32                                       propyl)benzyl]-3-(2,4,6-trichlorophenyl)-                                      urea                                                                           1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)-                                                                 .03      12    28                                       benzyl]-3-(4-chloro-2,6-dimethylphenyl)-                                       urea                                                                           1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-                                                             .03      25    46                                       3-(4-chloro-2,6-dimethylphenyl)urea                                            1-(n-Heptyl)-1-[4-(n-butyl)benzyl]-3-(4-                                                              .03      11    31                                       chloro-2,6-dimethylphenyl)urea                                                 1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethyl-                                                             .03      11    31                                       propyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                       phenyl)urea                                                                    1-(3,3-Dimethylbutyl)-1-benzyl-3-(4-                                                                  .03      51    64                                       chloro-2-methylphenyl)urea                                                     1-(n-Heptyl)-1-[4-(n-butyl)benzyl]-3-                                                                 .03      19    48                                       (4-chloro-2,5-dimethylphenyl)urea                                              1-(3,3-Dimethylbutyl)-1-(benzyl)-3-(4-                                                                .03      30    55                                       chloro-2,5-dimethylphenyl)urea                                                 1-(Isopentyl)-1-[4-(isopropyl)benzyl]-3-                                                              .03      37    49                                       (2,4-difluorophenyl)urea                                                       1-(Isopentyl)-1-[4-(isopropyl)benzyl]-3-                                                              .03      23    23                                       (4-chloro-2,6-dimethylphenyl)urea                                              1-(Isopentyl)-1-[4-(isopropyl)benzyl]-3-                                                              .03      35    31                                       (2,4,6-trifluorophenyl)urea                                                    1-(n-Heptyl)-1-[4-(isobutyl)benzyl]-3-                                                                .01      56    62                                       (4-chloro-2-methylphenyl)urea                                                  1-(n-Heptyl)-1-[4-(isopropyl)benzyl]-3-                                                               .01      64    77                                       (2,4-difluorophenyl)urea                                                       1-(n-Heptyl)-1-[4-(isopropyl)benzyl]-3-                                                               .01      20    35                                       (4-chloro-2,6-dimethylphenyl)urea                                              1-(n-Heptyl)-1-[4-(isopropyl)benzyl]-3-                                                               .01      75    60                                       (4-chloro-2-methylphenyl)urea                                                  1-(n-Heptyl)-1-[4-(isopropyl)benzyl]-3-                                                               .01      23    40                                       (2,4,6-trifluorophenyl)urea                                                    1-(n-Heptyl)-1-[4-(4-isopentyl)benzyl]-3-                                                             .01      17    20                                       (4-chloro-2-methylphenyl)urea                                                  1-(n-Heptyl)-1-[4-(isopentyl)benzyl]-3-                                                               .01      10    17                                       (4-chloro-2,6-dimethylphenyl)urea                                              1-(n-Heptyl)-1-[4-(2-acetoxyethyl)benzyl]-                                                            .003     60    55                                       3-(2,4-difluorophenyl)urea                                                     1-(n-Heptyl)-1-[4-(2-hydroxyethyl)benzyl]-                                                            .003     59    52                                       3-(2,4-difluorophenyl)urea                                                     1-(n-Heptyl)-1-[4-(4-hydroxybutyl)benzyl]-                                                            .01      26    24                                       3-(4-chloro-2,6-dimethylphenyl)urea                                            1-(n-Heptyl)-1-[4-(4-chlorobutyl)benzyl]-                                                             .03      18    19                                       3-(4-chloro-2,6-dimethylphenyl)urea                                            1-(n-Heptyl)-1-[4-(3-carboethoxypropyl)-                                                              .01      65    55                                       benzyl]-3-(4-chloro-2,6-dimethylphenyl)-                                       urea                                                                           1-(n-Heptyl)-1-[4-(3-methylbutoxy)benzyl)-                                                            .01      32    27                                       3-(2,4-difluorophenyl)urea                                                     1-(n-Heptyl)-1-[4-(4-ethylthiobutyl)-                                                                 .003     63    57                                       benzyl]-3-(4-chloro-2,6-dimethylphenyl)-                                       urea                                                                           1-(n-Heptyl)-1-[4-(4-isopropylthiobutyl)-                                                             .01      45    49                                       benzyl]-3-(4-chloro-2,6-dimethylphenyl)-                                       urea                                                                           1-(Isoheptyl)-1-[4-isopentyl)benzyl)-3-                                                               .003     45    24                                       (2,4-difluorophenyl)urea                                                       1-(Isoheptyl)-1-[4-(isopentyl)benzyl]-3-                                                              .001     40    40                                       (4-chloro-2,6-dimethylphenyl)urea                                              1-(Isoheptyl)-1-[4-(isopentyl)benzyl]-3-                                                              .001     45    33                                       (2,4,6-trifluorophenyl)urea                                                    1-(n-Heptyl)-1-[4-(2-ethylhexyl)benzyl]-3-                                                            .001     87    82                                       (2,4,6-trifluorophenyl)urea                                                    1-(n-Heptyl)-1-[4-(2-ethylhexyl)benzyl]-3-                                                            .001     87    83                                       4-chloro-2,6-dimethylphenyl)urea                                               1-(n-Heptyl)-1-[4-(2-ethylbutyl)benzyl]-3-                                                            .003     98    66                                       (2,4-difluorophenyl)urea                                                       1-(n-Heptyl)-1-[4-(2-ethylbutyl)benzyl]-3-                                                            .001     75    120                                      (2,4,6-trifluorophenyl)urea                                                    1-(n-Heptyl)-1-[4-(isohexyl)benzyl]-3-                                                                .003     53    45                                       (2,4-difluorophenyl)urea                                                       1-(n-Heptyl)-1-[4-(isohexyl)benzyl]-3-                                                                .001     73    64                                       (4-chloro-2,6-dimethylphenyl)urea                                              1-(n-Heptyl)-1-[4-(isohexyl)benzyl]-3-                                                                .001     78    77                                       (2,4,6-trifluorophenyl)urea                                                    1-(n-Heptyl)-1-[4-(cyclopentyl)benzyl]-3-                                                             .003     82    80                                       (2,4-difluorophenyl)urea                                                       1-(n-Heptyl)-1-[4-(cyclopentyl)benzyl]-3-                                                             003      36    35                                       (4-chloro-2,6-dichlorophenyl)urea                                              1-(n-Heptyl)-1-[4-(2-ethylhexyl)benzyl]-3-                                                            .003     56    63                                       (2,4-difluorophenyl)urea                                                       1-(n-Heptyl)-1-[4-(cyclopentyl)benzyl]-3-                                                             .001     58    69                                       (2,4,6-trifluorophenyl)urea                                                    1-(n-Heptyl)-1-[4-(2-ethylbutyl)benzyl]-3-                                                            .001     94    62                                       (4-chloro-2,6-dimethylphenyl)urea                                              1-(n-Heptyl)-1-[4-(2-methylpentyl)benzyl]-                                                            .003     72    53                                       3-(2,4-difluorophenyl)urea                                                     1-(n-Heptyl)-1-[4-(2-methylpentyl)benzyl]-                                                            .001     75    93                                       3-(2,4,6-trifluorophenyl)urea                                                  1-(n-Heptyl)-1-[4-(2-methylpentyl)benzyl]-                                                            .001     56    61                                       3-(4-chloro-2,6-dimethylphenyl)urea                                            1-(n-Heptyl)-1-[4-(3-methylpentyl)benzyl]-                                                            .001     89    72                                       3-(2,4-difluorophenyl)urea                                                     1-(n-Heptyl)-1-[4-(3-methylpentyl)benzyl]-                                                            .003     46    36                                       3-(2,4,6-trifluorophenyl)urea                                                  1-(n-Heptyl)-1-[4-(3-methylpentyl)benzyl]-                                                            .003     45    38                                       3-(4-chloro-2,6-dimethylphenyl)urea                                            1-(n-Heptyl)-1-[4-(cyclobutylmethyl)ben-                                                              .001     69    64                                       zyl]-3-(4-chloro-2,6-dimethylphenyl)urea                                       1-(n-Heptyl)-1-[4-(cyclopentylmethyl)ben-                                                             .003     50    62                                       zyl]-3-(2,4,6-trifluorophenyl)urea                                             1-(n-Heptyl)-1-[4-(cyclopentylmethyl)ben-                                                             .01      80    --                                       zyl]-3-(2,4-difluorophenyl)urea                                                1-(n-Heptyl)-1-[4-(cyclobutylmethyl)ben-                                                              .001     66    62                                       zyl]-3-(2,4,6-trifluorophenyl)urea                                             1-(n-Heptyl)-1-[4-(1,5-dimethylhexyl)ben-                                                             .001     88    83                                       zyl]-3-(2,4-difluorophenyl)urea                                                1-(n-Heptyl)-1-[4-(1,5-dimethylhexyl)ben-                                                             .001     100   94                                       zyl]-3-(4-chloro-2,6-dimethylphenyl)urea                                       1-(n-Heptyl)-1-[4-(1,5-dimethylhexyl)ben-                                                             .003     65    57                                       zyl]-3-(2,4,6-trifluoromethylphenyl)urea                                       1-(n-Heptyl)-1-[4-(cyclopentylmethyl)ben-                                                             .003     53    45                                       zyl]-3-(4-chloro-2,6-dimethylphenyl)urea                                       1-(n-Heptyl)-1-[4-(hydroxymethyl)benzyl]-                                                             .003     81    --                                       3-(2,4-difluorophenyl)urea                                                     1-(n-Heptyl)-1-[4-(acetoxymethyl)benzyl]-                                                             .01      70    --                                       3-(2,4-difluorophenyl)urea                                                     1-(n-Heptyl)-1-[4-(isopentyloxy)benzyl]-3-                                                            .001     23    25                                       (4-chloro-2,6-dimethylphenyl)urea                                              1-(n-Heptyl)-1-[4-(isopentyloxy)benzyl]-3-                                                            .001     61    69                                       (2,4-difluorophenyl)urea                                                       1-(n-Heptyl)-1-[4-(2-methylbutyl)benzyl]-                                                             .01      42    36                                       3-(2,4-difluorophenyl)urea                                                     1-(n-Heptyl)-1-[4-(2-methylbutyl)benzyl]-                                                             .001     64    76                                       3-(2,4,6-trifluorophenyl)urea                                                  1-(n-Heptyl)-1-[4-(2-isopropylthioethyl)-                                                             .003     51    49                                       benzyl]-3-(4-chloro-2,6-dimethylphenyl)-                                       urea                                                                           1-(n-Heptyl)-1-[4-(2-isopropylsulfonyl-                                                               .003     68    94                                       ethyl)benzyl]-3-(2,4-difluorophenyl)urea                                       1-(n-Heptyl)-1-[4-(2-isopropylsulfonyl-                                                               .003     54    57                                       ethyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                        phenyl)urea                                                                    1-(n-Heptyl)-1-[4-(2,3-dimethylpentyl)-                                                               .01      63    48                                       benzyl]-3-(2,4-difluorophenyl)urea                                             1-(n-Heptyl)-1-[4-(2-isopropylthioethyl)-                                                             .003     72    --                                       benzyl]-3-(2,4-difluorophenyl)urea                                             1-(n-Heptyl)-1-[4-(2-isopropylsulfinyl-                                                               .003     54    45                                       ethyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                        phenyl)urea                                                                    1-(n-Heptyl)-1-[4-(2,3-dimethylpentyl)-                                                               .01      31    33                                       benzyl]-3-(2,4,6-trifluorophenyl)urea                                          1-(n-Heptyl)-1-[4-(2,2-dimethylpropyl)-                                                               .01      51    22                                       benzyl]-3-(2,4-difluorophenyl)urea                                             1-(n-Heptyl)-1-[4-(2,2-dimethylpropyl)-                                                               .003     55    38                                       benzyl]-3-(2,4,6-trifluorophenyl)urea                                          1-(n-Heptyl)-1-[4-(2,2-dimethylpropyl)-                                                               .003     54    41                                       benzyl]-3-(4-chloro-2,6-dimethylphenyl)-                                       urea                                                                           1-(n-Heptyl)-1-[4-(2,3-dimethylpentyl)-                                                               .01      40    43                                       benzyl]-3-(4-chloro-2,6-dimethylphenyl)-                                       urea                                                                           1-(n-Heptyl)-1-[4-(2-isopropylsulfinyl-                                                               .003     84    --                                       ethyl)benzyl]-3-(2,4-difluorophenyl)urea                                       1-(n-Heptyl)-1-[4-(isopentyloxymethyl)-                                                               .01      60    --                                       benzyl]-3-(2,4-difluorophenyl)urea                                             1-(n-Heptyl)-1-[4-(isopentyloxymethyl)-                                                               .001     75    --                                       benzyl]-3-(2,4,6-trifluorophenyl)urea                                          1-(n-Heptyl)-1-[4-(isopentyloxymethyl)-                                                               .003     47    --                                       benzyl]-3-(4-chloro-2,6-dimethylphenyl)-                                       urea                                                                           ______________________________________                                    

The tests reported or shown in Tables I, II, III and IV, inclusive, have been actually carried out and the results therein actually obtained or concluded therefrom.

When the compounds are employed for the above utility, they may be combined with one or more pharmaceutically acceptable carriers, e.g., solvents, diluents, and the like, and may be administered orally in such forms as tablets, capsules, dispersible powders, granules, or suspensions containing, for example, from about 0.5% to 5% of suspending agent, syrups containing, for example, from about 10% to 50% of sugar, and elixirs containing, for example, from about 20% to 50% ethanol, and the like, or parenterally in the form of sterile injectable solutions or suspensions containing from about 0.5% to 5% suspending agent in an isotonic medium. These pharmaceutical preparations may contain, for example, from about 0.5% up to about 90% of the active ingredient in combination with the carrier, more usually between 5% and 60% by weight.

The antiatherosclerotic effective dosage of active ingredient employed may vary depending on the particular compound employed, the mode of administration, and the severity of the condition being treated. In general, however, satisfactory results are obtained when the compounds of the invention are administered at a daily dosage of from about 2 mg to about 500 mg/kg of animal body weight, preferably given in divided doses two to four times a day, or in sustained release form. For most large mammals, the total daily dosage is from about 100 mg to about 5,000 mg, preferably from about 100 mg to 2,000 mg. Dosage forms suitable for internal use comprise from about 25 to 500 mg of the active compound in intimate admixture with a solid or liquid pharmaceutically acceptable carrier. This dosage regimen may be adjusted to provide the optimal therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. A decided practical advantage is that these active compounds may be administered orally as well as by intravenous, intramuscular, or subcutaneous routes if necessary. Solid carriers include starch, lactose, dicalcium phosphate, microcrystalline cellulose, sucrose, and kaolin, while liquid carriers include sterile water, polyethylene glycols, non-ionic surfactants, and edible oils such as corn, peanut, and sesame oils, as are appropriate to the nature of the active ingredient and the particular form of administration desired. Adjuvants customarily employed in the preparation of pharmaceutical compositions may be advantageously included, such as flavoring agents, coloring agents, preserving agents, and antioxidants, e.g., vitamin E, ascorbic acid, BHT, and BHA.

The preferred pharmaceutical compositions from the stand-point of ease of preparation and administration are solid compositions, particularly tablets and hardfilled or liquid-filled capsules. Oral administration of the compounds is preferred.

These active compounds may also be administered parenterally or intraperitoneally. Solutions or suspensions of these active compounds as a free base or pharmacologically acceptable salt can be prepared in water suitably mixed with a surfactant such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms.

The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions In all cases, the form must be sterile and must be fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils.

The following examples describe in detail the chemical synthesis of representative compounds of the present invention. The procedures are illustrations, and the invention should not be construed as being limited by chemical reactions and conditions they express. No attempt has been made to optimize the yields obtained in these reactions, and it would be obvious to one skilled in the art that variations in reaction times, temperatures, solvents, and/or reagents could increase the yields.

EXAMPLE 1 1-Benzyl-1-(n-butyl)-3-(2,4-dimethylphenyl)urea

A solution of 4.89 g of 2,4-dimethylphenylisocyanate in 100 ml of hexane is added to a solution of 4.41 g of N-benzyl-n-butylamine in 150 ml of hexane, and the solution is stirred at room temperature for 2 hours and then evaporated. The residual solid is recrystallized from pentane to yield 1-benzyl-1-(n-butyl)-3-(2,4-dimethylphenyl)urea, m.p. 70°-71° C.

With reference to Example 1 and Table V, only those examples with listed identifying characteristics have been actually carried out. All other examples are simulated or predicted.

                                      TABLE V                                      __________________________________________________________________________     Example                                                                             Compound                           M.P. °C.                        __________________________________________________________________________     2    1-Benzyl-1-(n-butyl)-3-(2-methylphenyl)urea                                                                       48-53                                  3    1-Benzyl-1-(n-butyl)-3-(3-methylphenyl)urea                                                                       91-92                                  4    1-Benzyl-1-(n-butyl)-3-(4-methylphenyl)urea                                                                       102-103                                5    1-Benzyl-1-(n-butyl)-3-(3-ethylphenyl)urea                                6    1-Benzyl-1-(n-butyl)-3-(4-ethylphenyl)urea                                7    1-Benzyl-1-(n-butyl)-3-(4-isopropylphenyl)urea                            8    1-Benzyl-1-(n-butyl)-3-(4-n-butylphenyl)urea                              9    1-Benzyl-1-(n-butyl)-3-(2,3-dimethylphenyl)urea                                                                   77-78                                  10   1-Benzyl-1-(n-butyl)-3-(2,5-dimethylphenyl)urea                                                                   87-89                                  11   1-Benzyl-1-(n-butyl)-3-(2,6-dimethylphenyl)urea                                                                   125-126                                12   1-Benzyl-1-(n-butyl)-3-(3,4-dimethylphenyl)urea                                                                   94-95                                  13   1-Benzyl-1-(n-butyl)-3-(3,5-dimethylphenyl)urea                                                                   108-109                                14   1-Benzyl-1-(n-butyl)-3-(2,4,5-trimethylphenyl)urea                        15   1-Benzyl-1-(n-butyl)-3-(2,4,6-trimethylphenyl)urea                                                                141-144                                16   1-Benzyl-1-(n-butyl)-3-(4-methyoxyphenyl)urea                             17   1-Benzyl-1-(n-butyl)-3-(4-n-butoxyphenyl)urea                             18   1-Benzyl-1-(n-butyl)-3-(3,4,5-trimethoxyphenyl)urea                                                               144-145                                19   1-Benzyl-1-(n-butyl)-3-(4-methylthiophenyl)urea                           20   1-Benzyl-1-(n-butyl)-3-(2-chlorophenyl)urea                               21   1-Benzyl-1-(n-butyl)-3-(4-chlorophenyl)urea                               22   1-Benzyl-1-(n-butyl)-3-(2-bromophenyl)urea                                23   1-Benzyl-1-(n-butyl)-3-(4-bromophenyl)urea                                24   1-Benzyl-1-(n-butyl)-3-(4-fluorophenyl)urea                               25   1-Benzyl-1-(n-butyl)-3-(4-iodophenyl)urea                                 26   1-Benzyl-1-(n-butyl)-3-(2,3-dichlorophenyl)urea                           27   1-Benzyl-1-(n-butyl)-3-(2,4-dichlorophenyl)urea                           28   1-Benzyl-1-(n-butyl)-3-(2,5-dichlorophenyl)urea                           29   1-Benzyl-1-(n-butyl)-3-(3,4-dichlorophenyl)urea                                                                   102-105                                30   1-Benzyl-1-(n-butyl)-3-(3,5-dichlorophenyl)urea                                                                   100-103                                31   1-Benzyl-1-(n-butyl)-3-(2,4,6-trichlorophenyl)urea                                                                94-96                                  32   1-Benzyl-1-(n-butyl)-3-(2,4-difluorophenyl)urea                           33   1-Benzyl-1-(n-butyl)-3-(3-trifluoromethylphenyl)urea                                                              86-87                                  34   1-Benzyl-1-(n-butyl)-3-(3-acetylphenyl)urea                               35   1-Benzyl-1-(n-butyl)-3-(4-acetylphenyl)urea                               36   1-Benzyl-1-(n-butyl)-3-(4-carboethoxyphenyl)urea                          37   1-Benzyl-1-(n-butyl)-3-(4-phenoxyphenyl)urea                              38   1-Benzyl-1-(n-butyl)-3-(2-cyanophenyl)urea                                39   1-Benzyl-1-(n-butyl)-3-(3-chloro-2-methoxyphenyl)urea                                                             52-54                                  40   1-Benzyl-1-(n-butyl)-3-(5-chloro-4-methoxyphenyl)urea                                                             61-63                                  41   1-Benzyl-1-(n-butyl)-3-(2,6-dibromo-4-fluorophenyl)urea                   42   1-Benzyl-1-(n-butyl)-3-(2-nitro-4-methylphenyl)urea                       43   1-Benzyl-1-(n-butyl)-3-(3-chloro-4-methylphenyl)urea                                                              yellow oil                             44   1-Benzyl-1-(n-butyl)-3-(4-chloro-3-trifluoromethylphenyl)urea             45   1-Benzyl-1-(n-butyl)-3-(4-chloro-2-trifluoromethylphenyl)urea             46   1-Benzyl-1-(n-butyl)-3-(2-chloro-5-trifluoromethylphenyl)urea             47   1-Benzyl-1-(n-butyl)-3-(3,4-methylenedioxyphenyl)urea                     48   1-Benzyl-1-(n-butyl)-3-(4-phenylphenyl)urea                               49   1-Benzyl-1-(n-butyl)-3-(4-benzylphenyl)urea                               50   1-Benzyl-1-(sec-butyl)-3-(2,4-dimethylphenyl)urea                         51   1-Benzyl-1-(tert-butyl)-3-(4-methylphenyl)urea                            52   1-Benzyl-1-(n-hexyl)-3-(4-ethylphenyl)urea                                53   1-Benzyl-1-(n-heptyl)-3-(2-methylphenyl)urea                              54   1-Benzyl-1-(n-octyl)-3-(2-methylphenyl)urea                               55   1-Benzyl-1-(n-nonyl)-3-(4-carboethyloxyphenyl)urea                        56   1-Benzyl-1-(n-undecyl)-3-(2-methylphenyl)urea                             57   1-Benzyl-1-(n-tridecyl)-3-(4-methylphenyl)urea                            58   1-Benzyl-1-(n-tetradecyl)-3-(2-methylphenyl)urea                          59   1-Benzyl-1-(n-hexyldecyl)-3-(2-methylphenyl)urea                          60   1-Benzyl-1-(n-octadecyl)-3-(3-chlorophenyl)urea                           61   1-(2-Phenylethyl)-1-(sec-butyl)-3-(2,4-dimethylphenyl)urea                62   1-(2-Phenylethyl)-1-(n-hexyl)-3-(3-chloro-4-methylphenyl)urea             63   1-(2-Phenylethyl)-1-(n-heptyl)-3-(4-chlorophenyl)urea                     64   1-(2-Phenylethyl)-1-(n-ocyl)-3-(4-carboethoxyphenyl)urea                  65   1-(2-Phenylethyl)-1-(n-nonyl)-3-(2,4-dimethylphenyl)urea                  66   1-(2-Phenylethyl)-1-(n-decyl)-3-(2,4-dichlorophenyl)urea                  67   1-(2-Phenylethyl)-1-(n-undecyl)-3-(3-methylphenyl)urea                    68   1-(2-Phenylethyl)-1-(n-tridecyl)-3-(2-chlorophenyl)urea                   69   1-(2-Phenylethyl)-1-(n-hexadecyl)-3-(4-methylphenyl)urea                  70   1-(4-Phenyl-n-butyl)-1-(n-hexyl)-3-(3-methylphenyl)urea                   71   1-(4-Phenyl-n-butyl)-1-(n-heptyl)-3-(2,4-dimethylphenyl)urea              72   1-(4-Phenyl-n-butyl)-1-(n-octyl)-3-(4-methylphenyl)urea                   73   1-(4-Phenyl-n-butyl)-1-(n-nonyl)-3-(2,4-dichlorophenyl)urea               74   1-(4-Phenyl-n-butyl)-1-(n-decyl)-3-(3-chloro-4-methylphenyl)urea          75   1-(4-Phenyl-n-butyl)-1-(n-undecyl)-3-(4-chlorophenyl)urea                 76   1-(4-Phenyl-n-butyl)-1-(n-dodecyl)-3-(3-chlorophenyl)urea                 77   1-(4-Phenyl-n-butyl)-1-(n-tetradecyl)-3-(3-methylphenyl)urea              78   1-(4-Phenyl-n-butyl)-1-(n-octadecyl)-3-(2,4-dimethylphenyl)urea           79   1-Benzyl-1-(1,2-diphenylethyl)-3-(2,4-dimethylphenyl)urea                                                         157-158                                80   1-Benzyl-1-[1-(3-methoxyphenyl)-2-phenylethyl]-3-(2,4-dimethylphenyl)          -                                  124-126                                     urea                                                                      81   1-Benzyl-1-[1-(4-benzyloxyphenyl)-2-phenyl]-3-(2,4-dimethylphenyl)-                                               140-141                                     urea                                                                      82   N-(2,4-dimethylphenyl)-3,4-dihydro-1-(phenylmethyl)-2(1H)-isoquino-            linecarboxamide                                                           83   1-Benzyl-1-[1-(3-methoxyphenyl)-2-phenylethyl]-3-(3-trifluoromethyl-                                              125-126                                     phenyl)urea                                                               84   1-Benzyl-1-(2-phenylethyl)-3-(2,4-dimethylphenyl)urea                     85   1-Benzyl-1-(4-phenyl-n-butyl)-3-(2,4-dimethylphenyl)urea                  86   1-Benzyl-1-(n-pentyl)-3-(2,4-dimethylphenyl)urea                                                                  oil                                    87   1-Benzyl-1-(n-hexyl)-3-(2,4-dimethylphenyl)urea                                                                   oil                                    88   1-Benzyl-1-(n-octyl)-3-(2,4-dimethylphenyl)urea                                                                   oil                                    89   1-Benzyl-1-(n-undecyl)-3-(2,4-dimethylphenyl)urea                                                                 oil                                    90   1-Benzyl-1-(4-cyclohexyl-n-butyl)-3-(2,4-dimethylphenyl)urea              91   1-Benzyl-1-(cyclopentyl)-3-(2,4-dimethylphenyl)urea                       92   1-Benzyl-1-(1-naphthylmethyl)-3-(2,4-dimethylphenyl)urea                  93   1-Benzyl-1-(3-chlorobenzyl)-3-(2,4-dimethylphenyl)urea                    94   1-Benzyl-1-(4-chlorobenzyl)-3-(2,4-dimethylphenyl)urea                    95   1-Benzyl-1-[2-(4-chlorophenyl)ethyl]-3-(2,4-dimethylphenyl)urea           96   1-Benzyl-1-(2,4-dichlorobenzyl)-3-(2,4-dimethylphenyl)urea                97   1-Benzyl-1-(4-methoxybenzyl)-3-(2,4-dimethylphenyl)urea                   98   1-Benzyl-1-[2-(2-methoxyphenyl)ethyl]-3-(2,4-dimethylphenyl)urea          99   1-Benzyl-1-(4-methylbenzyl)-3-(2,4-dimethylphenyl)urea                    100  1-Benzyl-1-(3-methylbenzyl)-3-(2,4-dimethylphenyl)urea                    101  1-Benzyl-1-[2-(4-methylphenyl)ethyl]-3-(2,4-dimethylphenyl)urea           102  1-Benzyl-1-(2-phenylethyl)-3-(3-chloro-4-methylphenyl)urea                103  1-Benzyl-1-(4-phenyl-n-butyl)-3-(3-chloro-4-methylphenyl)urea             104  1-Benzyl-1-(n-heptyl)-3-(3-chloro-4-methylphenyl)urea                     105  1-Benzyl-1-(n-octyl)-3-(3-chloro-4-methylphenyl)urea                      106  1-Benzyl-1-(n-decyl)-3-(3-chloro-4-methylphenyl)urea                      107  1-Benzyl-1-(n-undecyl)-3-(3-chloro-4-methylphenyl)urea                    108  1-Benzyl-1-(n-tridecyl)-3-(3-chloro-4-methylphenyl)urea                   109  1-Benzyl-1-(n-tetradecyl)-3-(3-chloro-4-methylphenyl)urea                 110  1-Benzyl-1-(n-hexadecyl)-3-(3-chloro-4-methylphenyl)urea                  111  1-Benzyl-1-(n-octadecyl)-3-(3-chloro-4-methylphenyl)urea                  112  1-Benzyl-1-(cyclohexyl)-3-(3-chloro-4-methylphenyl)urea                   113  1-Benzyl-1-(1-naphthylmethyl)-3-(3-chloro-4-methylphenyl)urea             114  1-Benzyl-1-(4-chlorobenzyl)-3-(3-chloro-4-methylphenyl)urea               115  1-Benzyl-1-(4-methylbenzyl)-3-(3-chloro-4-methylphenyl)urea               116  1-Benzyl-1-(n-hexyl)-3-(4-methylphenyl)urea                               117  1-Benzyl-1-(n-octyl)-3-(4-methylphenyl)urea                               118  1-Benzyl-1-(n-undecyl)-3-(4-methylphenyl)urea                             119  1-Benzyl-1-(n-tetradecyl)-3-(4-methylphenyl)urea                          120  1-Benzyl-1-(n-hexyldecyl)-3-(4-methylphenyl)urea                          121  1-Benzyl-1-(n-octadecyl)-3-(4-methylphenyl)urea                           122  1-Benzyl-1-(1-naphthylmethyl)-3-(4-methylphenyl)urea                      123  1-Benzyl-1-(cyclopentyl)-3-(4-methylphenyl)urea                           124  1-Benzyl-1-(4-chlorobenzyl)-3-(4-methylphenyl)urea                        125  1-Benzyl-1-(4-methylbenzyl)-3-(4-methylphenyl)urea                        126  1-Benzyl-1-(n-pentyl)-3-(4-chlorophenyl)urea                              127  1-Benzyl-1-(n-heptyl)-3-(4-chlorophenyl)urea                              128  1-Benzyl-1-(n-nonyl)-3-(4-chlorophenyl)urea                               129  1-Benzyl-1-(n-decyl)-3-(4-chlorophenyl)urea                               130  1-Benzyl-1-(n-tridecyl)-3-(4-chlorophenyl)urea                            131  1-Benzyl-1-(n-tetradecyl)-3-(4-chlorophenyl)urea                          132  1-Benzyl-1-(n-hexadecyl)-3-(4-chlorophenyl)urea                           133  1-Benzyl-1-(1-naphthylmethyl)-3-(4-chlorophenyl)urea                      134  1-Benzyl-1-(cyclohexyl)-3-(4-chlorophenyl)urea                            135  1-Benzyl-1-(cyclopentyl)-3-(4-chlorophenyl)urea                           136  1-Benzyl-1-(4-chlorobenzyl)-3-(4-chlorophenyl)urea                        137  1-Benzyl-1-(3-chlorobenzyl)-3-(4-chlorophenyl)urea                        138  1-Benzyl-1-(4-methylbenzyl)-3-(4-chlorophenyl)urea                        139  1-Benzyl-1-(n-hexyl)-3-(3,4-dichlorophenyl)urea                           140  1-Benzyl-1-(n-octyl)-3-(3,4-dichlorophenyl)urea                           141  1-Benzyl-1-(n-undecyl)-3-(3,4-dichlorophenyl)urea                         142  1-Benzyl-1-(n-tetradecyl)-3-(3,4-dichlorophenyl)urea                      143  1-Benzyl-1-(n-octadecyl)-3-(3,4-dichlorophenyl)urea                       144  1-Benzyl-1-(cyclohexyl)-3-(3,4-dichlorophenyl)urea                        145  1-Benzyl-1-(1-naphthylmethyl)-3-(3,4-dichlorophenyl)urea                  146  1-Benzyl-1-(3-chlorobenzyl)-3-(3,4-dichlorophenyl)urea                    147  1-Benzyl-1-(4-chlorobenzyl)-3-(3,4-dichlorophenyl)urea                    148  1-Benzyl-1-(3-methylbenzyl)-3-(3,4-dichlorophenyl)urea                    149  1-Benzyl-1-(4-methylbenzyl)-3-(3,4-dichlorophenyl)urea                    150  1-Benzyl-1-(n-butyl)-3-(3-phenyl)thiourea                                                                         83-85                                  151  1-Benzyl-1-(n-butyl)-3-(2-methylphenyl)thiourea                           152  1-Benzyl-1-(n-butyl)-3-(3-methylphenyl)thiourea                           153  1-Benzyl-1-(n-butyl)-3-(4-methylphenyl)thiourea                           154  1-Benzyl-1-(n-butyl)-3-(3-ethylphenyl)thiourea                            155  1-Benzyl-1-(n-butyl)-3-(4-ethylphenyl)thiourea                            156  1-Benzyl-1-(n-butyl)-3-(4-isopropylphenyl)thiourea                        157  1-Benzyl-1-(n-butyl)-3-(4-n-butylphenyl)thiourea                          158  1-Benzyl-1-(n-butyl)-3-(2,3-dimethylphenyl)thiourea                       159  1-Benzyl-1-(n-butyl)-3-(2,5-dimethylphenyl)thiourea                       160  1-Benzyl-1-(n-butyl)-3-(2,6-dimethylphenyl)thiourea                       161  1-Benzyl-1-(n-butyl)-3-(3,4-dimethylphenyl)thiourea                       162  1-Benzyl-1-(n-butyl)-3-(3,5-dimethylphenyl)thiourea                       163  1-Benzyl-1-(n-butyl)-3-(2,4,5-trimethylphenyl)thiourea                    164  1-Benzyl-1-(n-butyl)-3-(2,4,6-trimethylphenyl)thiourea                    165  1-Benzyl-1-(n-butyl)-3-(4-methoxyphenyl)thiourea                          166  1-Benzyl-1-(n-butyl)-3-(2,4-dimethoxyphenyl)thiourea                      167  1-Benzyl-1-(n-butyl)-3-(3-methylthiophenyl)thiourea                       168  1-Benzyl-1-(n-butyl)-3-(2-chlorophenyl)thiourea                           169  1-Benzyl-1-(n-butyl)-3-(3-chlorophenyl)thiourea                           170  1-Benzyl-1-(n-butyl)-3-(4-chlorophenyl)thiourea                           171  1-Benzyl-1-(n-butyl)-3-(2-bromophenyl)thiourea                            172  1-Benzyl-1-(n-butyl)-3-(4-bromophenyl)thiourea                            173  1-Benzyl-1-(n-butyl)-3-(4-fluorophenyl)thiouera                           174  1-Benzyl-1-(n-butyl)-3-(4-iodophenyl)thiourea                             175  1-Benzyl-1-(n-butyl)-3-(2,3-dichlorophenyl)thiourea                       176  1-Benzyl-1-(n-butyl)-3-(2,4-dichlorophenyl)thiourea                       177  1-Benzyl-1-(n-butyl)-3-(2,5-dichlorophenyl)thiourea                       178  1-Benzyl-1-(n-butyl)-3-(3,5-dichlorophenyl)thiourea                       179  1-Benzyl-1-(n-butyl)-3-(2,4,6-trichlorophenyl)thiourea                    180  1-Benzyl-1-(n-butyl)-3-(2,4-difluorophenyl)thiourea                       181  1-Benzyl-1-(4-phenyl-n-butyl)-3-(2,4-dimethylphenyl)thiourea              182  1-Benzyl-1-(n-hexyl)-3-(2,4-dimethylphenyl)thiourea                       183  1-Benzyl-1-(n-undecyl)-3-(2,4-dimethylphenyl)thiourea                     184  1-Benzyl-1-(n-tetradecyl)-3-(2,4-dimethylphenyl)thiourea                  185  1-Benzyl-1-(n-hexadecyl)-3-(2,4-dimethylphenyl)thiourea                   186  1-Benzyl-1-(4-cyclohexyl-n-butyl)-3-(2,4-dimethylphenyl)thiourea          187  1-Benzyl-1-(cyclopentyl)-3-(2,4-dimethylphenyl)thiourea                   188  1-Benzyl-1-(1-naphthylmethyl)-3-(2,4-dimethylphenyl)thiourea              189  1-Benzyl-1-(3-chlorobenzyl)-3-(2,4-dimethylphenyl)thiourea                190  1-Benzyl-1-(4-chlorobenzyl)-3-(2,4-dimethylphenyl)thiourea                191  1-Benzyl-1-[2-(4-chlorophenyl)ethyl]-3-(2,4-dimethylphenyl)thiourea       192  1-Benzyl-1-(2,4-dichlorobenzyl)-3-(2,4-dimethylphenyl)thiourea            193  1-Benzyl-1-(4-methoxybenzyl)-3-(2,4-dimethylphenyl)thiourea               194  1-Benzyl-1-[2-(2-methoxyphenyl)ethyl]-3-(2,4-dimethylphenyl)thiourea      195  1-Benzyl-1-(4-methylbenzyl)-3-(2,4-dimethylphenyl)thiourea                196  1-Benzyl-1-(3-methylbenzyl)-3-(2,4-dimethylphenyl)thiourea                197  1-Benzyl-1-[2-(4-methylphenyl)ethyl]-3-(2,4-dimethylphenyl)thiourea       198  1-Benzyl-1-(2-phenylethyl)-3-(3-chloro-4-methylphenyl)thiourea            199  1-Benzyl-1-(4-phenyl-n-butyl)-3-(3-chloro-4-methylphenyl)thiourea         200  1-Benzyl-1-(n-heptyl)-3-(3-chloro-4-methylphenyl)thiourea                 201  1-Benzyl-1-(n-octyl)-3-(3-chloro-4-methylphenyl)thiourea                  202  1-Benzyl-1-(n-butyl)-3-(3-chloro-2-methoxyphenyl)urea                                                             52-54                                  203  1-Benzyl-1-(n-butyl)-3-(5-chloro-2-methoxyphenyl)urea                                                             161-163                                204  1-(n-Butyl)-1-(2-fluorobenzyl)-3-(2,4-dimethylphenyl)urea                                                         76-77                                  205  1-(n-Butyl)-1-(4-fluorobenzyl)-3-(2,4-dimethylphenyl)urea                                                         78-79                                  206  1-(n-Butyl)-1-(2-chlorobenzyl)-3-(2,4-dimethylphenyl)urea                                                         101-102                                207  1-(n-Butyl)-1-(2,6-dichlorobenzyl)-3-(2,4-dimethylphenyl)urea                                                     145-146                                208  1-(4-Bromobenzyl)-1-(n-butyl)-3-(2,4-dimethylphenyl)urea                                                          61-63                                  209  1-(n-Butyl)-1-(4-n-butylbenzyl)-3-(2,4-dimethylphenyl)urea                                                        60-62                                  210  1-(n-Butyl)-1-(4-methylbenzyl)-3-(2,4-dimethylphenyl)urea                                                         oil                                    211  1-(n-Butyl)-1-(4-tert-butylbenzyl)-3-(2,4-dimethylphenyl)urea                                                     28-31                                  212  1-(n-Butyl)-1-(4-chlorobenzyl)-3-(2,4-dimethylphenyl)urea                                                         oil                                    213  1-(n-Butyl)-1-(4-methoxybenzyl)-3-(2,4-dimethylphenyl)urea                                                        oil                                    214  1-(n-Butyl)-1-(3,4-methylenedioxybenzyl)-3-(2,4-dimethylphenyl)urea                                               oil                                    215  1-(n-Butyl)-1-(4-trifluoromethylbenzyl)-3-(2,4-dimethylphenyl)urea                                                oil                                    216  1-(n-Butyl)-1-(4-phenylbenzyl)-3-(2,4-dimethylphenyl)urea                                                         82-83                                  217  1-(n-Butyl)-1-(2-phenylethyl)-3-(2,4-dimethylphenyl)urea                                                          oil                                    218  1-(n-Butyl)-1-[2-(4-fluorophenyl)ethyl]-3-(2,4-dimethylphenyl)urea                                                oil                                    219  1-(n-Butyl)-1-[2-(4-chlorophenyl)ethyl]-3-(2,4-dimethylphenyl)urea                                                oil                                    220  1-(n-Butyl)-1-[2-(3-methoxyphenyl)ethyl]-3-(2,4-dimethylphenyl)urea                                               oil                                    221  1-(n-Butyl)-1-(3-phenylpropyl)-3-(2,4-dimethylphenyl)urea                                                         oil                                    222  1-(n-Butyl)-1-[4-(n-pentyl)benzyl]-3-(2,4-dimethylphenyl)urea                                                     65-67                                  223  1-(n-Butyl)-1-[4-(n-hexyl)benzyl]-3-(2,4-dimethylphenyl)urea                                                      oil                                    224  1-(n-Butyl)-1-(3-chlorobenzyl)-3-(2,4-dimethylphenyl)urea                                                         oil                                    225  1-(n-Butyl)-1-[4-(n-butoxy)benzyl]-3-(2,4-dimethylphenyl)urea                                                     oil                                    226  1-(n-Butyl)-1-[4-(n-pentyloxy)benzyl]-3-(2,4-dimethylphenyl)urea                                                  oil                                    227  1-(n-Butyl)-1-[4-(n-hexyloxy)benzyl]-3-(2,4-dimethylphenyl)urea                                                   oil                                    228  1-(n-Butyl)-1-[4-(n-heptyloxy)benzyl]-3-(2,4-dimethylphenyl)urea                                                  oil                                    229  1-(n-Butyl)-1-(4-nitrobenzyl)-3-(2,4-dimethylphenyl)urea                                                          oil                                    230  1-(n-Butyl)-1-[2-(2-methylphenyl)ethyl]-3-(2,4-dimethylphenyl)urea                                                102-103                                231  1-(n-Butyl)-1-[2-(3-methylphenyl)ethyl]-3-(2,4-dimethylphenyl)urea                                                oil                                    232  1-(n-Butyl)-1-[2-(4-methylphenyl)ethyl]-3-(2,4-dimethylphenyl)urea                                                oil                                    233  1-(n-Butyl)-1-[2-(4-ethoxyphenyl)ethyl]-3-(2,4-dimethylphenyl)urea                                                oil                                    234  1-(n-Butyl)-1-[2-(3-fluorophenyl)ethyl]-3-(2,4-dimethylphenyl)urea                                                oil                                    235  1-(n-Butyl)-1-[2-(2-chlorophenyl)ethyl]-3-(2,4-dimethylphenyl)urea                                                oil                                    236  1-(n-Butyl)-1-[2-(3-chlorophenyl)ethyl]-3-(2,4-dimethylphenyl)urea                                                oil                                    237  1-(n-Butyl)-1-[2-(4-bromophenyl)ethyl]-3-(2,4-dimethylphenyl)urea                                                 oil                                    238  1-(n-Butyl)-1-[2-(3,4-dimethoxyphenyl)ethyl-3-(2,4-dimethyl-                                                      oil                                         phenyl)urea                                                               239  1-(n-Butyl)-1-(2-adamantylethyl)-3-(2,4-dimethylphenyl)urea                                                       134-135                                240  1-(n-Butyl)-1-(3-cyclohexyl-2-phenylethyl)-3-(2,4-dimethylphenyl)urea          .                                  112-113                                241  1-(n-Butyl)-1-(di-(4-chlorophenyl)ethyl)-3-(2,4-dimethylphenyl)urea                                               145-147                                242  1-(n-Butyl)-1-(2,4-dichlorobenzyl)-3-(2,4-dimethylphenyl)urea                                                     120-121                                243  1-(n-Butyl)-1-(3-trifluoromethylbenzyl)-3-(4-fluorobenzyl)-3-(2,4-di-                                             114-115                                     methylphenyl)urea                                                         244  1-(4-Chlorobenzyl)-1-(1-naphthylmethyl-3-(2,4-dimethylphenyl)urea                                                 134-136                                245  1-(4-Methoxybenzyl)-1-(2,4-dichlorobenzyl)-3-(2,4-dimethylphenyl)urea                                             124-126                                246  1-(3-Chlorobenzyl)-1-(4-methoxybenzyl)-3-(2,4-dimethylphenyl)urea                                                 108-109                                247  1-(4-Phenylbenzyl)-1-(3,4-dichlorobenzyl)-3-(2,4-dimethylphenyl)urea                                              103-105                                248  1-(2-Flourobenzyl)-1-(4-methylbenzyl)-3-(2,4-dimethylphenyl)urea                                                  128-130                                249  1-(4-Chlorobenzyl)-1-(3,4-dimethoxybenzyl)-3-(2,4-dimethylphenyl)urea                                             94-96                                  250  1-(4-Fluorobenzyl)-1-(3,4-methylenedioxybenzyl)-3-(2,4-dimethyl-                                                  122-124                                     phenyl)urea                                                               251  1-(n-Butyl)-1-(4-methylthiobenzyl)-3-(2,4-dimethylphenyl)urea                                                     oil                                    252  1-(2,4-Dichlorobenzyl)-1-(4-methylthiobenzyl)-3-(2,4-dimethyl-                                                    124-125                                     phenyl)urea                                                               253  1-[2-(3,4-Dimethoxyphenyl)ethyl]-1-(3,4-methylenedioxybenzyl)-3-(2,4-                                             oil                                         dimethylphenyl)urea                                                       254  1-[2-(2-Methylphenyl)ethyl]-1-(2,4-dichlorobenzyl)-3-(2,4-dimethyl-                                               120-122                                     phenyl)urea                                                               255  1-[2-(4-Methylphenyl)ethyl]-1-(4-chlorobenzyl)-3-(2,4-dimethyl-                                                   oil                                         phenyl)urea                                                               256  1-[2-(4-Ethoxyphenyl)ethyl]-1-(2-chlorobenzyl)-3-(2,4-dimethyl-                                                   oil                                         phenyl)urea                                                               257  1-[2-(3-Fluorophenyl)ethyl]-1-(3-methoxybenzyl)-3-(2,4-dimethyl-                                                  94-95                                       phenyl)urea                                                               258  1-[2-(3-Methoxyphenyl)ethyl]-1-(3-chlorobenzyl)-3-(2,4-dimethyl-                                                  73-74                                       phenyl)urea                                                               259  1-(3,3-Diphenylpropyl)-1-(4-fluorobenzyl)-3-(2,4-dimethylphenyl)urea                                              109-110                                260  1-(n-Butyl)-1-(3,3-diphenylpropyl)-3-(2,4-dimethylphenyl)urea                                                     94-95                                  261  1-(n-Butyl)-1-(4-cyclohexylbutyl)-3-(2,4-dimethylphenyl)urea                                                      oil                                    262  1-[2-(3,4-Dimethoxyphenyl)ethyl]-1-(3-chloro-4-methylbenzyl)-3-                                                   gum                                         (2,4-dimethylphenyl)urea                                                  263  1-[2-(2-Methylphenyl)ethyl]-1-(4-bromobenzyl)-3-(2,4-dimethyl-                                                    126-127                                     phenyl)urea                                                               264  1-[2-(3-Trifluoromethylphenyl)ethyl]-1-(2-chlorobenzyl)-3-(2,4-                                                   115-117                                     dimethylphenyl)urea                                                       265  1-(2-Fluorobenzyl)-1-(2-methoxybenzyl)-3-(2,4-dimethylphenyl)urea                                                 96-98                                  266  1-[2-(3,4-Dimethoxyphenyl)ethyl]-1-(4-fluorobenzyl)-3-(2,4-dimethyl-                                              gum                                         phenyl)urea                                                               267  1-[2-(4-Ethoxyphenyl)ethyl]-1-(2,4-dimethylbenzyl)-3-(2,4-dimethyl-                                               gum                                         phenyl)urea                                                               268  1-[2-(3-Methylphenyl)ethyl]-1-(3-nitrobenzyl)-3-(2,4-dimethyl-                                                    99-101                                      phenyl)urea                                                               269  1-[2-(2,5-Dimethoxyphenyl)ethyl]-1-(3-chlorobenzyl)-3-(2,4-dimethyl-                                              86-88                                       phenyl)urea                                                               270  1-(n-Butyl)-1-(2-methyl-2,2-diphenyl)ethyl-3-(2,4-dimethylphenyl)urea                                             159-160                                271  1-(n-Butyl)-1-(4-hexyloxybenzyl)-3-(2,4,6-trimethylphenyl)urea                                                    90-91                                  272  1-(n-Butyl)-1-(4-heptyloxybenzyl)-3-(2,4,6-trimethylphenyl)urea                                                   86-87                                  273  1-(n-Butyl)-1-benzyl-3-(4-trifluoroacetylamino-3,5-dichloro-                                                      173-175                                     phenyl)urea                                                               274  1-Benzyl-1-(4-n-butylbenzyl)-3-(2,4-dimethylphenyl)urea                                                           oil                                    275  1-Benzyl-1-(4-n-butylbenzyl)-3-(2,4,6-trimethylphenyl)urea                                                        oil                                    276  1-Benzyl-1-(4-n-butylbenzyl)-3-(4-butylphenyl)urea                                                                yellow oil                             277  1-Benzyl-1-(4-n-butylbenzyl)-3-(4-phenoxyphenyl)urea                                                              79-80                                  278  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4-dimethylphenyl)urea                                                       yellow oil                             279  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4,5-trimethylphenyl)urea                                                    yellow oil                             280  1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphenyl)ethyl]-3-(2,4,5-trimethyl-                                              157-158                                     phenyl)urea                                                               281  1-(n-Heptyl)-1-(4-n-butyloxybenzyl)-3-(2,4-dimethylphenyl)urea                                                    oil                                    282  1-(n-Heptyl)-1-(4-n-butyloxybenzyl)-3-(2,4,5-trimethylphenyl)urea                                                 yellow oil                             283  1-Benzyl-1-(4-butyloxybenzyl)-3-(2,4-dimethylphenyl)urea                                                          solid                                  284  1-Benzyl-1-(4-butyloxybenzyl)-3-(2,4,5-trimethylphenyl)urea                                                       solid                                  285  1-Benzyl-1-(4-butylbenzyl)-3-(2,4,5-trimethylphenyl)urea                                                          yellow oil                             286  1-Benzyl-1-[2-(phenyl-1-(4-benzyloxyphenyl)ethyl]-3-(2,4,6-trimethyl-                                             140-141                                     phenyl)urea                                                               287  1-(n-Heptyl)-1-(4-n-butyloxybenzyl)-3-(2,4,6-trichlorophenyl)urea                                                 63-64                                  288  1-(n-Heptyl)-(4-n-butyloxybenzyl)-3-(2,4-dichlorophenyl)urea                                                      gum                                    289  1-(n-Heptyl)-(4-n-butoxybenzyl)-3-(2-trifluoromethyl-4-chloro-                                                    gum                                         phenyl)urea                                                               290  1-Benzyl-1-(4-n-butoxybenzyl)-3-(2,4,6-trichlorophenyl)urea                                                       91-93                                  291  1-Benzyl-1-(4-n-butoxybenzyl)-3-(2,4-dichlorophenyl)urea                                                          gum                                    292  1-Benzyl-1-(4-n-butoxybenzyl)-3-(2-trifluoromethyl-4-chloro-                                                      gum                                         phenyl)urea                                                               293  1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-(3-trifluoromethylphenyl)urea                                                 gum                                    294  1-(n-Benzyl)-1-(4-n-butoxybenzyl)-3-(3-trifluoromethylphenyl)urea                                                 gum                                    295  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4-dichlorophenyl)urea                                                       gum                                    296  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2-trifluoromethyl-4-chloro-                                                   gum                                         phenyl)urea                                                               297  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4,6-trichlorophenyl)urea                                                    gum                                    298  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(3-trifluoromethylphenyl)urea                                                  gum                                    299  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2,4,5-trichlorophenyl)urea                                                    gum                                    300  1-Benzyl-1-(4-n-butoxybenzyl)-3-(2-methyl-4-chlorophenyl)urea                                                     107-108                                301  1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-(2,4-difluorophenyl)urea                                                      gum                                    302  1-(n-Heptyl)-1-(4-n-butoxybenzyl)-3-(2-methyl-4-chlorophenyl)urea                                                 gum                                    303  1-(n-Heptyl)-1-(2-furyl)-3-(2,4,5-trimethylphenyl)urea                                                            65-67                                  304  1-(n-Heptyl)-1-(2-furyl)-3-(2,4,6-trichlorophenyl)urea                                                            yellow oil                             305  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2-methyl-4-chlorophenyl)urea                                                  oil                                    306  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(4-carboethoxyphenyl)urea                                                      65-66                                  307  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(2-methylphenyl)urea                                                           oil                                    308  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(3-methylphenyl)urea                                                           oil                                    309  1-(n-Heptyl)-1-(4-n-butylbenzyl)-3-(4-carboxyphenyl)urea                                                          147-149                                310  1-(n-Heptyl)-1-(2-phenylethyl)-3-(2-methyl-4-chlorophenyl)urea                                                    gum                                    311  1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4,5-trichlorophenyl)urea                                                      gum                                    312  1-(n-Heptyl)-1-(2-phenylethyl)-3-(2-trifluoromethyl-4-chloro-                                                     gum                                         phenyl)urea                                                               313  1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4-dimethylphenyl)urea                                                         gum                                    314  1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4-dichlorophenyl)urea                                                         gum                                    315  1-(n-Heptyl)-1-(2-phenylethyl)-3-(2,4-difluorophenyl)urea                                                         gum                                    316  1-(n-Heptyl)-1-(2-phenylethyl)-3-(3-trifluoromethylphenyl)urea                                                    gum                                    317  1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphenyl)ethyl]-3-(2,4,6-tri-                                                    131-133                                     chlorophenyl)urea                                                         318  1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxybenzyl)-3-(2,4,6-trichloro-                                                  oil                                         phenyl)urea                                                               319  1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxybenzyl)-3-(2,4-dichloro-                                                     oil                                         phenyl)urea                                                               320  1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxybenzyl)-3-(2,4,5-trichloro-                                                  oil                                         phenyl)urea                                                               321  1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxybenzyl)-3-(2-trifluoromethyl-                                                oil                                         4-chlorophenyl)urea                                                       322  1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxybenzyl)-3-(3-trifluoromethyl-                                                oil                                         phenyl)urea                                                               323  1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxybenzyl)-3-(2,4-difluoro-                                                     oil                                         phenyl)urea                                                               324  1-(4-n-Pentylbenzyl)-1-(4-n-pentyloxybenzyl)-3-(2-methyl-4-chloro-                                                oil                                         phenyl)urea                                                               325  1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-(2,4,6-trichlorophenyl)urea                                             157-159                                326  1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-(2-methyl-4-chloro-                                                     168-169                                     phenyl)urea                                                               327  1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-(2,4-difluorophenyl)urea                                                122-124                                328  1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-(3-trifluoromethyl-                                                     127-129                                     phenyl)urea                                                               329  1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-(2,4,5-trichlorophenyl)urea                                             110-113                                330  1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphenyl)ethyl]-3-(2,4,5-trichloro-                                              142-145                                     phenyl)urea                                                               331  1-Benzyl-1-(4-n-butyloxybenzyl)-3-(2,4,5-trichlorophenyl)urea                                                     oil                                    332  1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphenyl)ethyl]-3-(2,4-difluoro-                                                 84-85                                       phenyl)urea                                                               333  1-Benzyl-1-(4-n-butoxybenzyl)-3-(2,4-difluorophenyl)urea                                                          oil                                    334  1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphenyl)ethyl]-3-(2,4-dichloro-                                                 126-128                                     phenyl)urea                                                               335  1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphenyl)ethyl]-3-(2-trifluoro-                                                  99-101                                      methyl-4-chlorophenyl)urea                                                336  1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphenyl)ethyl]-3-(3-trifluoro-                                                  102-104                                     methylphenyl)urea                                                         337  1-Benzyl-1-[2-phenyl-1-(4-benzyloxyphenyl)ethyl]-3-(2-methyl-4-                                                   125-126                                     chlorophenyl)urea                                                         338  1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-(2,4-dichlorophenyl)urea                                                96-98                                  339  1-(4-Chlorobenzyl)-1-(1-naphthylmethyl)-3-(2-trifluoromethyl-4-                                                   yellow glass                                chlorophenyl)urea                                                         340  1-[2-(4-Methylphenyl)ethyl]-1-(3-chlorobenzyl)-3-(2,4-dimethyl-                                                   34-35                                       phenyl)urea                                                               341  1-(n-Butyl)-1-benzyl-3-(3-chloro-2-hydroxyphenyl)urea                                                             59-62                                  342  1-[2-(3-Fluorophenyl)ethyl]-1-(4-methylbenzyl)-3-(2,4-dimethyl-                                                   74-75                                       phenzyl)urea                                                              343  1-(n-Butyl)-1-benzyl-3-(2-nitrophenyl)urea                                                                        yellow oil                             344  1-(3,4-Methylenedioxyphenyl)-1-(3,3-diphenylpropyl)-3-(2,4-                                                       135-137                                     dimethylphenyl)urea                                                       345  1-(n-Butyl)-1-[3-(3,4-dimethoxyphenyl)propyl]-3-(2,4-dimethyl-                                                    yellow oil                                  phenyl)urea                                                               346  1-(3,4-Dimethylbenzyl)-1-(2-chlorobenzyl)-3-(2,4-dimethylphenyl)urea                                              113-115                                347  1-(n-Butyl)-1-benzyl-3-(2-hydroxy-5-chlorophenyl)urea                                                             113-115                                348  1-(3,4-Dimethoxybenzyl)-1-[2-(4-methylphenyl)ethyl]-3-(2,4-di-                                                    gum                                         methylphenyl)urea                                                         349  1-(n-Butyl)-1-benzyl-3-(4-amino-3,5-dichlorophenyl)urea                                                           121-124                                350  1-(n-Butyl)-1-(benzyl)-3-[4-(chloroacetamido)-3,5-dichloro-                                                       135-138                                     phenyl)urea                                                               351  1-[2-(2-Chlorophenyl)ethyl]-1-(3,4-dimethylbenzyl)-3-(2,4-dimethyl-                                               96-98                                       phenyl)urea                                                               352  1-[2-(2-Chlorophenyl)ethyl]-1-(3-methylbenzyl)-3-(2,4-dimethyl-                                                   92-95                                       phenyl)urea                                                               353  1-(n-Butyl)-1-benzyl-3-(4-chloro-2-methylphenyl)urea                                                              83-84                                  354  1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)benzyl]-3-(4-chloro-2-methyl-                                                 88-91                                       phenyl)urea                                                               355  1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)benzyl]-3-(4-chloro-2-methyl-                                                106-107                                     phenyl)urea                                                               356  1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)benzyl]-3-(2,4,6-trichloro-                                                  114-115                                     phenyl)urea                                                               357  1-(3,3-Dimethylbutyl)-1-[4-(n-butoxy)benzyl]-3-(2,4-difluoro-                                                     oil                                         phenyl)urea                                                               358  1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)benzyl]-3-(2,4-difluoro-                                                      oil                                         phenyl)urea                                                               359  1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)benzyl]-3-(2,4,6-trichloro-                                                   solid                                       phenyl)urea                                                               360  1-(5,5-Dimethylhexyl)-1-[4-(n-butyl)benzyl]-3-(4-chloro-2-methyl-                                                 oil                                         phenyl)urea                                                               361  1-(5,5-Dimethylhexyl)-1-[4-(n-butyl)benzyl]-3-(2,4-difluoro-                                                      oil                                         phenyl)urea                                                               362  1-(5,5-Dimethylhexyl-1-[4-(n-butyl)benzyl]-3-(2,4,6-trichloro-                                                    oil                                         phenyl)urea                                                               363  1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-3-(4-chloro-2-methyl-                                                    110-111                                     phenyl)urea                                                               364  1-(3,3-Dimethylbutyl)-1-benzyl-3-(2,4-difluorophenyl)urea                                                         82-84                                  365  1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-3-(2,4-difluorophenyl)urea                                               67-70                                  366  1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-3-(2,4,6-trichloro-                                                      148-149                                     phenyl)urea                                                               367  1-(n-Heptyl)-1-[4-(n-butyl)benzyl]-3-(4-trifluoromethylphenyl)urea                                                69-71                                  368  1-(3,3,-Dimethylbutyl)-1-[4-(n-butyl)benzyl]-3-(4-trifluoromethyl-                                                103-104                                     phenyl)urea                                                               369  1-(3,3-Dimethylbuty)-1-(4-chlorobenzyl)-3-(4-trifluoromethyl-                                                     140-141                                     phenyl)urea                                                               370  1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethylpropyl)benzyl]-3-(2,4-                                                    oil                                         difluorophenyl)urea                                                       371  1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethylpropyl)benzyl]-3-(4-chloro-                                               125-130                                     2-methylphenyl)urea                                                       372  1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethylpropyl)benzyl]-3-(2,4,6-                                                  glass                                       trichlorophenyl)urea                                                      373  1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)benzyl]-3-(4-chloro-2,6-                                                      138-139                                     dimethylphenyl)urea                                                       374  1-(3,3-Dimethylbutyl)-1-(4-chlorobenzyl)-3-(4-chloro-2,6-dimethyl-                                                178-180                                     phenyl)urea                                                               375  1-(n-Heptyl)-1-[4-(n-butyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                                      48-50                                       phenyl)urea                                                               376  1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethylpropyl)benzyl]-3-(4-chloro-                                               148-150                                     2,6-dimethylphenyl)urea                                                   377  1-(3,3-Dimethylbutyl)-1-benzyl-3-(4-chloro-2-methylphenyl)urea                                                    114-115                                378  1-(n-Heptyl)-1-[4-(n-butyl)benzyl]-3-(4-chloro-2,5-dimethyl-                                                      oil                                         phenyl)urea                                                               379  1-(3,3-Dimethylbutyl)-1-(benzyl)-3-(4-chloro-2,5-dimethylphenyl)urea                                              solid                                  380  1-(3,3-Dimethylbutyl)-1-[4-(n-butyl)benzyl]-3-(4-chloro-2,5-dimethyl-                                             102-103                                     phenyl)urea                                                               381  1-(3,3-Dimethylbutyl)-1-[4-(2,2-dimethylpropyl)benzyl]-3-(4-chloro-                                               160-161                                     2,5-dimethylphenyl)urea                                                   382  1-[(4-butylphenyl)methyl]-1-[3,3-dimethylbutyl]-3-[2,4,6-trifluoro-                                               oil                                         phenyl]urea                                                               383  1-[(4-butylphenyl)methyl]-1-(n-heptyl)-3-[2,4,6-trifluorophenyl]urea                                              35-36                                  384  1-[(4-butoxyphenyl)methyl]-1-[3,3-dimethylbutyl]-3-[2,4,6-trifluoro-           phenyl]urea                                                               385  1-[(4-butoxyphenyl)methyl]-1-(n-heptyl)-3-[2,4,6-trifluorophenyl]urea     386  1-Benzyl-1-[3,3-dimethylbutyl]-3-[2,4,6-trifluorophenyl]urea                                                      108-110                                387  1-Benzyl-1-(n-heptyl)-3-[2,4,6-trifluorophenyl]urea                       388  1-[3,3-dimethylbutyl]-1-[[4-(2,2-dimethylpropyl)phenyl]methyl]-3-                                                 39-40                                       [2,4,6-trifluorophenyl]urea                                               389  1-[(4-chlorophenyl)methyl]-1-[3,3-dimethylbutyl]-3-[2,4,6-trifluoro-           phenyl]urea                                                               390  1-(n-Heptyl)-1-[4-(2,2-dimethylpropyl)phenylmethyl]-3-(2,4-difluoro-                                              40-46                                       phenyl)urea                                                               391  1-(n-Heptyl)-1-[4-(2,2-dimethylpropyl)phenylmethyl]-3-(4-chloro-2,6-                                              111-113                                     dimethylphenyl)urea                                                       392  1-(n-Heptyl)-1-[4-(2,2-dimethylpropyl)phenylmethyl]-3-(2,4,6-tri-                                                 oil                                         fluorophenyl)urea                                                         393  1-(n-Heptyl)-1-(4-isobutylphenylmethyl)-3-(2,4-difluorophenyl)urea        394  1-(n-Heptyl)-1-(4-isobutylphenylmethyl)-3-(4-chloro-2,6-dimethyl-                                                 87-88                                       phenyl)urea                                                               395  1-(n-Heptyl)-1-(4-isobutylphenylmethyl)-3-(2,4,6-trifluorophenyl)urea                                             73-74                                  396  1-(n-Heptyl)-1-(4-isopentylphenylmethyl)-3-(2,4-difluorophenyl)urea                                               oil                                    397  1-(n-Heptyl)-1-(4-isopentylphenylmethyl)-3-(4-chloro-2,6-dimethyl-                                                oil                                         phenyl)urea                                                               398  1-(n-Heptyl)-1-(4-isopentylphenylmethyl)-3-(2,4,6-trifluorophenyl)-                                               oil                                         urea                                                                      399  1-(6-Hydroxyheptyl)-1-[4-(2,2-dimethylpropyl)benzyl]-3-(4-chloro-2,6-                                             oil                                         dimethylpyhenyl)urea                                                      400  1-(Isopentyl)-1-[4-(isopropyl)benzyl]-3-(2,4-difluorophenyl)urea                                                  oil                                    401  1-(Isopentyl)-1-[4-(isopropyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                                   115-117                                     phenyl)urea                                                               402  1-(Isopentyl)-1-[4-(isopropyl)benzyl]-3-(2,4,6-trifluorophenyl)urea                                               oil                                    403  1-(6-Hydroxyheptyl)-1-[4-(2,2-dimethylpropyl)benzyl]-3-(2,4-di-                                                   oil                                         fluorophenyl)urea                                                         404  1-(n-Heptyl)-1-[4-(isobutyl)benzyl]-3-(4-chloro-2-methylphenyl)urea                                               oil                                    405  1-(n-Heptyl)-1-[4-(isopropyl)benzyl]-3-(2,4-difluorophenyl)urea                                                   oil                                    406  1-(n-Heptyl)-1-[  4-(isopropyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                                  121-123                                     phenyl)urea                                                               407  1-(n-Heptyl)-1-[4-(isopropyl)benzyl]-3-(4-chloro-2-methylphenyl)urea                                              oil                                    408  1-(n-Heptyl)-1-[4-(isopropyl)benzyl]-3-(2,4,6-trifluorophenyl)urea                                                60-61                                  409  1-(n-Heptyl)-1-[4-(4-isopentyl)benzyl]-3-(4-chloro-2-methylphenyl)-                                               oil                                         urea                                                                      410  1-(n-Heptyl)-1-[4-isopentyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                                     48-52                                       phenyl)urea                                                               411  1-(n-Heptyl)-1-[4-(2-acetoxyethyl)benzyl]-3-(2,4-difluorophenyl)urea                                              oil                                    412  1-(n-Heptyl)-1-[4-(2-hydroxyethyl)benzyl]-3-(2,4-difluorophenyl)urea                                              oil                                    413  1-(n-Heptyl)-1-[4-carbomethoxymethyl)benzyl]-3-(2,4-difluorophenyl)-                                              oil                                         urea                                                                      414  1-(n-Heptyl)-1-[4-(carboxymethyl)benzyl]-3-(2,4-difluorophenyl)urea                                               solid                                  415  1-(n-Heptyl)-1-[4-(4-hydroxybutyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                               65-66                                       phenyl)urea                                                               416  1-(n-Heptyl)-1-[4-(3-carboxypropyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                              oil                                         phenyl)urea                                                               417  1-(n-Heptyl)-1-[4-(4-chlorobutyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                                oil                                         phenyl)urea                                                               418  1-(n-Heptyl)-1-[4-(3-carboethoxypropyl)benzyl]-3-(4-chloro-2,6-                                                   oil                                         dimethylphenyl)urea                                                       419  1-(n-Heptyl)-1-[4-(3-methylbutoxy)benzyl]-3-(2,4-difluorophenyl)urea                                              oil                                    420  1-(n-Heptyl)-1-[4-(4-ethylthiobutyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                             47-52                                       phenyl)urea                                                               421  1-(n-Heptyl)-1-[4-(4-isopropylthiobutyl)benzyl]-3-(4-chloro-2,6-                                                  40-44                                       dimethylphenyl)urea                                                       422  1-(Isoheptyl)-1-[4-(isopentyl)benzyl]-3-(2,4-difluorophenyl)urea                                                  oil                                    423  1-(Isoheptyl)-1-[4-(isopentyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                                   84-86                                       phenyl)urea                                                               424  1-(Isoheptyl)-1-[4-(isopentyl)benzyl]-3-(2,4,6-trifluorophenyl)urea                                               oil                                    425  1-(n-Heptyl)-1-[4-(4-isopropylthiobutyl)benzyl]-3-(2,4-difluoro-                                                  oil                                         phenyl)urea                                                               426  1-(n-Heptyl)-1-[4-(isohexyloxybenzyl]-3-(2,4-difluorophenyl)urea                                                  oil                                    427  1-(n-Heptyl)-1-[4-(2-ethylhexyl)benzyl]-3-(2,4,6-trifluorophenyl)urea                                             oil                                    428  1-(n-Heptyl)-1-[4-(2-ethylhexyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                                 oil                                         phenyl)urea                                                               429  1-(n-Heptyl)-1-[4-(2-ethylbutyl)benzyl]-3-(2,4-difluorophenyl)urea                                                oil                                    430  1-(n-Heptyl)-1-[4-(2-ethylbutyl)benzyl]-3-(2,4,6-trifluorophenyl)urea          8                                  oil                                    431  1-(n-Heptyl)-1-[4-(isohexyl)benzyl]-3-(2,4-difluorophenyl)urea                                                    oil                                    432  1-(n-Heptyl)-1-[4-(isohexyl)benzyl]-3-(4-chloro-2,6-dimethylphenyl)-                                              56-61                                       urea                                                                      433  1-(n-Heptyl)-1-[4-(isohexyl)benzyl]-3-(2,4,6-trifluorophenyl)urea                                                 oil                                    434  1-(n-Heptyl)-1-[4-(cyclopentyl)benzyl]-3-(2,4-difluorophenyl)urea                                                 oil                                    435  1-(n-Heptyl)-1-[4-(cyclopentyl)benzyl]-3-(4-chloro-2,6-dichloro-                                                  119-121                                     phenyl)urea                                                               436  1-(n-Heptyl)-1-[4-(2-ethylhexyl)benzyl]-3-(2,4-difluorophenyl)urea                                                oil                                    437  1-(n-Heptyl)-1-[4-(cyclopentyl)benzyl]-3-(2,4,6-trifluorophenyl)urea                                              solid                                  438  1-(n-Heptyl)-1-[4-(2-ethylbutyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                                 oil                                         phenyl)urea                                                               439  1-(n-Heptyl)-1-[4-(2-methylpentyl)benzyl]-3-(2,4-difluorophenyl)urea                                              oil                                    440  1-(n-Heptyl)-1-[4-(2-methylpentyl)benzyl]-3-(2,4,6-trifluorophenyl)-                                              oil                                         urea                                                                      441  1-(n-Heptyl)-1-[4-(2-methylpentyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                               oil                                         phenyl)urea                                                               442  1-(n-Heptyl)-1-[4-(3-methylpentyl)benzyl]-3-(2,4-difluorophenyl)urea                                              oil                                    443  1-(n-Heptyl)-1-[4-(3-methylpentyl)benzyl]-3-(2,4,6-trifluorophenyl)-                                              oil                                         urea                                                                      444  1-(n-Heptyl)-1-[4-(3-methylpentyl)benzyl]-3-(4-chloro-2,6-dimethyl-                                               oil                                         phenyl)urea                                                               445  1-(n-Heptyl)-1-[4-(cyclobutylmethyl)benzyl]-3-(4-chloro-2,6-dimethyl-          2                                  solid                                       phenyl)urea                                                               446  1-(n-Heptyl)-1-[4-(cyclobutylmethyl)benzyl]-3-(2,4-difluorophenyl)-                                               oil                                         urea                                                                      447  1-(n-Heptyl)-1-[4-(cyclopentylmethyl)benzyl]-3-(2,4,6-trifluoro-                                                  solid                                       phenyl)urea                                                               448  1-(n-Heptyl)-1-[4-(4-cyclopentylmethyl)benzyl]-3-(2,4-difluoro-                                                   oil                                         phenyl)urea                                                               449  1-(n-Heptyl)-1-[4-(cyclobutylmethyl)benzyl]-3-(2,4,6-trifluoro-                                                   solid                                       phenyl)urea                                                               450  1-(n-Heptyl)-1-[4-(1,5-dimethylhexyl)benzyl]-3-(2,4-difluorophenyl)-                                              oil                                         urea                                                                      451  1-(n-Heptyl)-1-[4-(1,5-dimethylhexyl)benzyl]-3-(4-chloro-2,6-                                                     oil                                         dimethylphenyl)urea                                                       452  1-(n-Heptyl)-1-[4-(1,5-dimethylhexyl)benzyl]-3-(2,4,6-trifluoro-                                                  oil                                         methylphenyl)urea                                                         453  1-(n-Heptyl)-1-[4-(cyclopentylmethyl)benzyl]-3-(4-chloro-2,6-                                                     109-111                                     dimethylphenyl)urea                                                       454  1-(n-Heptyl)-1-[4-(hydroxymethyl)benzyl]-3-(2,4-difluorophenyl)urea                                               oil                                    455  1-(n-Heptyl)-1-[4-(acetoxymethyl)benzyl]-3-(2,4-difluorophenyl)urea                                               65-71                                  456  1-(n-Heptyl)-1-[4-(isopentyloxy)benzyl]-3-(4-chloro-2,6-dimethyl-                                                 82-85                                       phenyl)urea                                                               457  1-(n-Heptyl)-1-[4-(isopentyloxy)benzyl]-3-(2,4-difluorophenyl)urea                                                oil                                    458  1-(n-Heptyl)-1-[4-(2-methylbutyl)benzyl]-3-(2,4-difluorophenyl)urea                                               oil                                    459  1-(n-Heptyl)-1-[4-(2-methylbutyl)benzyl]-3-(2,4,6-trifluorophenyl)-                                               solid                                       urea                                                                      460  1-(n-Heptyl)-1-[4-(2-isopropylthioethyl)benzyl]-3-(4-chloro-2,6-                                                  112-113                                     dimethylphenyl)urea                                                       461  1-(n-Heptyl)-1-[4-(2-isopropylsulfonylethyl)benzyl]-3-(2,4-difluoro-                                              oil                                         phenyl)urea                                                               462  1-(n-Heptyl)-1-[4-(2-isopropylsulfonylethyl)benzyl]-3-(4-chloro-2,6-                                              130-131                                     dimethylphenyl)urea                                                       463  1-(n-Heptyl)-1-[4-(2,3-dimethylpentyl)benzyl]-3-(2,4-difluorophenyl)-                                             oil                                         urea                                                                      464  1-(n-Heptyl)-1-[4-(2-isopropylthioethyl)benzyl]-3-(2,4-difluoro-                                                  oil                                         phenyl)urea                                                               465  1-(n-Heptyl)-1-[4-(2-isopropylsulfinylethyl)benzyl]-3-(4-chloro-2,6-                                              oil                                         dimethylphenyl)urea                                                       466  1-(n-Heptyl)-1-[4-(2,3-dimethylpentyl)benzyl]-3-(2,4,6-trifluoro-                                                 oil                                         phenyl)urea                                                               467  1-(n-Heptyl)-1-[4-(1,2-dimethylpropyl)benzyl]-3-(2,4-difluorophenyl)-                                             32-34                                       urea                                                                      468  1-(n-Heptyl)-1-[4-(1,2-dimethylpropyl)benzyl]-3-(2,4,6-trifluoro-                                                 69-70                                       phenyl)urea                                                               469  1-(n-Heptyl)-1-[4-(1,2-dimethylpropyl)benzyl]-3-(4-chloro-2,6-                                                    108-110                                     dimethylphenyl)urea                                                       470  1-(n-Heptyl)-1-[4-(2,3-dimethylpentyl)benzyl]-3-(4-chloro-2,6-                                                    oil                                         dimethylphenyl)urea                                                       471  1-(n-Heptyl)-1-[4-(2-isopropylsulfinylethyl)benzyl]-3-(2,4-difluoro-                                              oil                                         phenyl)urea                                                               472  1-(n-Heptyl)-1-[4-(isopentyloxymethyl)benzyl]-3-(2,4-difluorophenyl)-                                             oil                                         urea                                                                      473  1-(n-Heptyl)-1-[4-(isopentyloxymethyl)benzyl]-3-(2,4,6-trifluoro-                                                 oil                                         phenyl)urea                                                               474  1-(n-Heptyl)-1-[4-(isopentyloxymethyl)benzyl]-3-(4-chloro-2,6-                                                    oil                                         dimethylphenyl)urea                                                       __________________________________________________________________________

EXAMPLE 475 1-Benzyl-1-(n-butyl)-3-(3-chlorophenyl)urea

A solution of 1.56 g of phenyl chloroformate in 50 ml of ether was added dropwise to a stirred solution of 2.55 g of 3-chloroaniline in 35 ml of ether. The mixture was stirred for one hour at room temperature and then filtered. The filtrate was evaporated and the residue crystallized from hexane to yield phenyl N-(3-chlorophenyl)carbamate.

A solution of 1.46 g of phenyl N-(3-chlorophenyl)carbamate in 15 ml of tetrahydrofuran was added to a solution of 1.92 g of N-benzyl-n-butylamine in 20 ml of tetrahydrofuran and the mixture stirred under reflux for hours. The mixture was diluted with hexane and the precipitate collected by filtration. Recrystallization from pentane afforded 1-benzyl-1-(n-butyl)-3-(3-chlorophenyl)urea, m.p. 69°-70° C.

EXAMPLE 476 1-Benzyl-1-(n-butyl)-3-(4-carboxyphenyl)urea

A solution of 5.30 g of 1-benzyl-1-(n-butyl)-3-(4-carboethoxyphenyl)urea in 100 ml of ethanol is treated with 25 ml of 1N aqueous sodium hydroxide, stirred under reflux for 16 hours, allowed to cool, acidified with 1N hydrochloric acid, and filtered. The solid is recrystallized from ethanol to yield 1-benzyl-1-(n-butyl)-3-(4-carboxyphenyl)urea as a white solid.

EXAMPLE 477 1-Benzyl-1-(n-butyl)-3-(2-hydroxy-3-chlorophenyl)urea

A solution of 1.73 g of 1-benzyl-1-(n-butyl)-3-(2-methoxy-3-chlorophenyl)urea and 1.0 ml of boron tribromide in 40 ml of methylene chloride was stirred at ambient temperature for 3 days and diluted with water. The organic layer was separated, dried, and evaporated. The residue was crystallized from hexane to yield 1-benzyl1-(n-butyl)-3-(2-hydroxy-3-chlorophenyl)urea, m.p. 59°-62° C.

EXAMPLE 478 N-(2-Chlorobenzyl)-3-methoxyphenylacetamide

A mixture of 12.5 g of 3-methoxyphenylacetic acid, 21.2 g of 2-chlorobenzylamine, 15.1 g of triethylamine, 19.3 ml of borontrifluoride etherate, and 500 ml of toluene was stirred under reflux for 18 hours using a Dean-Stark moisture trap and allowed, to cool. The mixture was extracted with aqueous sodium hydroxide, dilute hydrochloric acid, and water. The remaining organic solution was then evaporated and the residue crystallized from hexane to yield N-(2-chlorobenzyl)-3-methoxyphenylacetamide as a yellow solid, m.p. 89°-91° C.

EXAMPLE 479 N-(n-Butyl)-2-chlorobenzylamine

A solution of 21.2 g of N-(n-butyl)-2-chlorobenzamide in 100 ml of tetrahydrofuran was added with cooling to 200 ml of 1M borane in tetrahydrofuran and the mixture was stirred under reflux for 18 hours, allowed to cool, and treated with 6N hydrochloric acid. The organic solvent was evaporated, and the residue was partitioned between ether and aqueous sodium hydroxide solution. The ether layer was separated, dried, and evaporated. The residue was distilled to yield N-(n-butyl)-2-chlorobenzylamine as a colorless liquid, b.p. 65°-75° C. at 60μ.

EXAMPLE 480 4-Butyl-N-(6-hydroxyhexyl)benzamide

To a stirred solution of 23.5 g of 6-amino-1-hexanol and 30 g of triethylamine in 200 ml of dichloromethane, cooled in an ice bath, was added dropwise a solution of 43.3 g of p-butylbenzoyl chloride in 100 ml of dichloromethane. The mixture was allowed to stir at room temperature for 16 hours. Then the mixture was washed in succession with water, saturated sodium carbonate, water, and finally brine. The organic layer was dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was triturated, filtered, and rinsed with cold hexane and gave 47.5 g of the desired product in 61% yield as a beige solid, m.p. 80°-81° C.

Additional amides (Examples 481-486), which are listed in Table VI, were prepared according to the procedure of Example 480.

                                      TABLE VI                                     __________________________________________________________________________     Example                                                                             Amide                Description                                                                             MP or BP                                                                               % Yield                             __________________________________________________________________________     481  4-Butyl- .sub.-- N-[2-(2-hydroxyethoxy)ethyl]-                                                      Yellow Oil       93                                       benzamide                                                                 482   .sub.-- N-Heptyl-2-furancarboxamide                                                                Colorless Liquid                                                                        121° C./0.1 mm                                                                  99                                  483  4-Butoxy- .sub.-- N-(2-thienylmethyl)benzamide                                                      White Crystals                                                                          128-130° C.                                                                     72                                  484   .sub.-- N-(2-Thienylmethyl)heptanamide                                                             Colorless Solid                                                                         62-63° C.                                                                       82                                  485   .sub.-- N-[(4-Butylphenyl)methyl]-5-(trimethyl-                                                    White Solid                                                                             72-74° C.                                                                       55                                       silyl)pentanamide                                                         486  3,3-Dimethylbutyl-2-thiophenecarboxamide                                                            White Solid                                                                             145-146° C.                                                                     91                                  __________________________________________________________________________

EXAMPLE 487 6-[[(4-Butylphenyl)methyl]amino]-1-hexanol

To a solution of 45.0 g of the product of Example 1 in 200 ml of tetrahydrofuran, cooled in an ice bath was added dropwise, 325 ml of borane (1M boranetetrahydrofuran complex). The resulting mixture was heated at reflux for 16 hours. The mixture was cooled to room temperature and 57 ml of 6N hydrochloric acid was added dropwise over argon gas. The solvent was evaporated in vacuo. The residue was slurried in water while adding sodium hydroxide pellets until the pH was basic. The aqueous solution was extracted with diethyl ether. The etheral extract was dried over anhydrous sodium sulfate, then evaporated in vacuo, and gave 33.7 g of the desired product in 79% yield, as a yellow oil.

EXAMPLE 488 4-Butyl-N-[5-(trimethylsilyl)pentyl]benzenemethanamine

To a suspension of 2.5 g of lithium aluminum hydride in 100 ml of anhydrous tetrahydrofuran was added dropwise a solution of 5.0 g of N-[(4-butylphenyl)methyl]5-(trimethylsilyl)pentanamide in tetrahydrofuran. The resulting mixture was heated at reflux for 16 hours. The mixture was cooled, and the complex was decomposed by the cautious portionwise addition of sodium sulfate decahydrate. The mixture was stirred for 1/2 hour and then filtered. The solid was washed with tetrahydrofuran, and the filtrate was dried with anhydrous magnesium sulfate and filtered. The filtrate was evaporated to dryness and gave 4.53 g of the desired product as a colorless liquid, in 95% yield.

EXAMPLE 489 3,3-Dimethylbutyl-2-thiophenemethanamine

To a solution of 17.0 ml of Vitride® T [sodium dihydrobis(2-methoxyethoxy)aluminate (70% solution in toluene)] in 50 ml of toluene, was added dropwise a solution of 5.0 g of 3,3-dimethylbutyl-2-thiophene carboxamide in 50 ml of dried tetrahydrofuran. The resulting mixture was heated at reflux for 2 hours, then cooled. The complex was decomposed by adding dropwise 30 ml of 2.5N sodium hydroxide. The mixture was stirred for one hour. The layers were separated and the organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated in vacuo and gave a light brown liquid. Kugelrohr distillation (75° C./0.15 mm of mercury) gave 4.0 g (82% yield) of the desired product.

Additional secondary amines are listed in Table VII and were prepared by the procedures described in Examples 487-489.

                                      TABLE VII                                    __________________________________________________________________________          Example                                                                              Amide                               %                               Example                                                                             Procedure                                                                            Precursor                                                                            Amine         Description                                                                          MP or BP  Yield                           __________________________________________________________________________     490  487   Ex. 482                                                                               .sub.-- N-Heptyl-2-furanmethan-                                                             Colorless                                                                            70-75° C./0.08                                                                    67                                               amine         Liquid                                          491  488   Ex. 485                                                                              4-Butyl- .sub.-- N-[5-(trimethyl-                                                            Colorless       95                                               silyl)pentyl]benzenemeth-                                                                    Liquid                                                           anamine                                                       492  487   Ex. 481                                                                              2-[2-[[(4-Butylphenyl)-                                                                      Colorless       83                                               methyl]amino]ethoxy]-                                                                        Liquid                                                           ethanol                                                       493  488   Ex. 484                                                                               .sub.-- N-Heptyl-2-thiopenemeth-                                                            Colorless                                                                            90-100° C./0.20                                                                   96                                               anamine       Liquid                                          494  488   Ex. 483                                                                               .sub.-- N-[(4-Butoxyphenyl)meth-                                                            Colorless       92                                               yl]-2-thiophenemethanamine                                                                   Liquid                                          __________________________________________________________________________

EXAMPLE 495 1-[(4-Butylphenyl)methyl]-3-(2,4-dimethylphenyl)-1(6-hydroxyhexyl)urea

To a stirred solution of 1.46 g of 2,4-dimethylphenyl isocyanate in 100 ml of hexane was added a solution of 2.63 g of 6-[[(4-butylphenyl)methyl]amino]-1-hexanol (prepared as described in Example 489), in 500 ml of hexane. The mixture was stirred at room temperature for 2 hours. Evaporation gave a gum. The gum was purified by chromatography to yield 2.81 g of the desired product as a colorles gum.

Additional ureas and thioureas of the present invention were prepared by the reaction of an appropriate arylisocyanate or arylisothiocyanate with a hereinbefore prepared secondary amine by the method of Example 495. The compounds appear in Table VIII.

                                      TABLE VIII                                   __________________________________________________________________________          Amine                          MP or BP %                                 Example                                                                             Precursor                                                                            Product           Description                                                                           °C.                                                                              Yield                             __________________________________________________________________________     496  Ex. 490                                                                              1-(2-Furanylmethyl)-1-heptyl-3-                                                                  White Solid                                                                           65-67    86                                           (2,4,6-trimethylphenyl)urea                                         497  Ex. 490                                                                              1-(2-Furanylmethyl)-1-heptyl-3-                                                                  Yellow Oil                                                                            135-140/0.175 mm                                                                        87                                           (2,4,6-trichlorophenyl)urea                                         498  Ex. 487                                                                              1-[(4-Butylphenyl)methyl]-3-(4-                                                                  Colorless       58                                           chloro-2-methylphenyl)-1-(6-hydroxy-                                                             Oil                                                          hexyl)urea                                                          499  Ex. 487                                                                              1-[(4-Butylphenyl)methyl]-1-(6-                                                                  Colorless       63                                           hydroxyhexyl)-3-(2,4,5-trimethyl-                                                                Gum                                                          phenyl)urea                                                         500  Ex. 492                                                                              1-[(Butylphenyl)methyl]-3-(2,4-                                                                  Colorless       46                                           dimethylphenyl)-1-[2-(2-hydroxy-                                                                 Gum                                                          ethoxy)ethyl]urea                                                   501  Ex. 492                                                                              1-[(4-Butylphenyl)methyl]-1-[2-(2-                                                               White Solid                                                                           84-86    89                                           hydroxyethoxy)ethyl]-3-(2,4,5-tri-                                             methylphenyl)urea                                                   502  Ex. 493                                                                              1-Heptyl-1-(2-thienylmethyl)-3-                                                                  White Solid                                                                           84-85    94                                           (2,4,5-trimethylphenyl)urea                                         503  Ex. 493                                                                              1-Heptyl-1-(2-thienylmethyl)-3-                                                                  White Solid                                                                           72-73    72                                           (2,4,6-trichlorophenyl)urea                                         504  Ex. 494                                                                              1-[(4-Butoxyphenyl)methyl]-1-(2-                                                                 White Solid                                                                           114-115  99                                           thienylmethyl)-3-(2,4,5-trimethyl-                                             phenyl)urea                                                         505  Ex. 487                                                                              1-[(4-Butylphenyl)methyl]-1-(6-                                                                  Light Brown     65                                           hydroxyhexyl)-3-(2,4,6-trichloro-                                                                Oil                                                          phenyl)urea                                                         506  Ex. 491                                                                              1-[(4-Butylphenyl)methyl]-3-(4-                                                                  Colorless                                                                             165-170/0.080 mm                                                                        77                                           chloro-2-methylphenyl)-1-[5-(tri-                                                                Oil                                                          methylsilyl)pentyl]urea                                             507  Ex. 491                                                                              1-[(4-Butylphenyl)methyl]-3-(2,4-                                                                Colorless                                                                             165/0.080 mm                                                                            82                                           difluorophenyl)-1-[5-(trimethyl-                                                                 Oil                                                          silyl)pentyl)urea                                                   508  Ex. 489                                                                              3-(2,4-Difluorophenyl)-1-(3,3-di-                                                                Colorless                                                                             75/0.150 mm                                                                             73                                           methylbutyl)-1-(2-thienylmethyl)urea                                                             Liquid                                            509  Ex. 489                                                                              3-(4-Chloro-2-methylphenyl)-1-(3,3-                                                              White Solid                                                                           111-113  64                                           dimethylbutyl)-1-(2-thienylmethyl)-                                            urea                                                                510  Ex. 489                                                                              1-(3,3-Dimethylbutyl)-1-(2-thienyl-                                                              White Solid                                                                           118-120  91                                           methyl)-3-(2,4,6-trichlorophenyl)-                                             urea                                                                __________________________________________________________________________

Other ureas and thioureas which may be prepared by the method described in Example 495 include:

-[(4-Butylphenyl)methyl]-3-[(2-methoxy-5-methyl)phenyl]-1-[5-(trimethylsilyl)pentyl]urea

1-[(4-Butylphenyl)methyl]-3-[(4-carboethoxy-2-methyl)phenyl]-1-[5-(trimethylsilyl)pentyl]urea

1-[(4-n-Butylphenyl)methyl]-3-[(4-carboxy-2-methyl)phenyl]-1-[5-(trimethylsilyl)pentyl]urea

EXAMPLE 511 Phenyl-N-(2 4-difluorophenyl)carbamate

To a solution of 1.94 g of 2,4-difluoroaniline in 20 ml of toluene was added dropwise 1.29 g of phenyl chloroformate. The mixture was stirred for 15 minutes, washed with three 10 ml portions of water, dried over anhydrous sodium sulfate, and filtered through a pad of diatomaceous earth. The filtrate was evaporated in vacuo to give an oil which solidified on cooling. The solid was crystallized from hexane to give 1.73 g of the desired product as pale tan crystals in 93% yield, mp 82°-84° C.

EXAMPLE 512 1-[(4-Butylphenyl)methyl]-3-(2,4-difluorophenyl)-1(6-hydroxyhexyl)urea

A mixture of 1.58 g of 6-[[(4-butylphenyl)methyl]amino]-1-hexanol and 1.5 g of phenyl-N-(2,4-difluorophenyl)carbamate in 40 ml of toluene was heated at reflux for 5 hours. The reaction mixture was cooled and allowed to stand at room temperature for 16 hours. The solution was washed with 3N aqueous hydrochloric acid, brine, 1N aqueous sodium hydroxide and brine again, then was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated in vacuo and gave a yellow oil. The oil was treated by preparative high pressure liquid chromatography and gave 0.93 g (37%) of the desired product as a colorless oil.

EXAMPLE 513 Phenyl[(4-butylphenyl)methyl][6-hydroxyhexyl]carbamate

To a stirred solution of 7.26 g of 6-[[(4-butylphenyl)methyl]amino]-1-hexanol in 50 ml of toluene was added a solution of 2.16 g of phenyl chloroformate in 20 ml of toluene, with the immediate precipitation of a white solid. The resulting mixture was stirred at room temperature for 24 hours. The mixture was filtered, and the filter was washed with toluene. The combined filtrate and wash was evaporated in vacuo and gave a colorless oil. The oil was Kugelrohr distilled and gave 3.5 g of the desired product in 66% yield as a colorless oil, bp 180°-195° C./0.06 mm of mercury.

EXAMPLE 514 5-(Trimethylsilyl)pentanoic acid

Preparation of Grignard reagent:

To a suspension of 1.58 g of magnesium turnings in 7.0 ml of freshly distilled tetrahydrofuran (distilled over benzophenone and sodium metal) was added about 2.0 ml of bromomethyltrimethylsilane under argon. A few crystlas of iodine were added and the mixture was heated with a hot air gun. The reaction began immediately and an additional amount of bromomethyltrimethylsilane (for a total of 10.03 g) was added dropwise over a 20 minute period. The mixture was stirred and heated at an oil bath temperature of 70°-80° C. for an additional 3 hours, then cooled at room temperature and allowed to stand.

In another flask a solution of 9.02 g of 4-bromobutyric acid in 30 ml of dry, freshly distilled, tetrahydrofuran was stirred and cooled at -30° C. under argon, the 19.0 ml of methyl magnesium chloride was added to the solution while maintaining the temperature at -20° C. The mixture was stirred at -20° C. for 10 minutes, then a solution of dilithium tetrachlorocuprate (prepared by dissolving 85.4 mg of lithium chloride and 173 mg of cupric chloride in 8.0 ml of tetrahydrofuran) was added to the reaction mixture, and stirring was continued for 5 minutes longer at -20° C. Then the hereinabove prepared Grignard reagent in 7.0 ml of tetrahydrofuran (kept in solution by warming) was added dropwise at -20° C. The resulting mixture was stirred at -20° C. for one hour more, then at ambient temperature for 16 hours.

The reaction mixture was then poured into a mixture of ethyl acetate:10% sulfuric acid (200 ml:200 ml) and stirred for 5 minutes. The two layers were separated and the organic layer was washed three times with brine, dried over anhydrous magnesium sulfate and filtered. The volatiles were evaporated in vacuo to leave a brown liquid. The liquid was distilled using a Vigreux column and an oil bath temeprature of 150°-160° C. for the third fraction which gave 7.5 g of the desired product (bp 139°-139.5° C./10 mm) as a pinkish liquid (80% yield).

EXAMPLE 515 1-[(4-Butylphenyl)methyl]-1-[6-[(methylsulfonyl)oxy]hexyl]-3-[(2,4,5-trimethylphenyl)methyl]urea

To a cooled solution (0°-5° C.) of 10.0 g of 1-[(4-butylphenyl)methyl]-1-6-(hydroxyhexyl)-3-(2,4,5-trimethylphenyl)urea and 7.3 ml (5.3 g) of triethylamine in 125 ml of dichloromethane was added dropwise a solution of 2.4 ml of methanesulfonyl chloride in 25 ml of dichloromethane. The resulting solution was gradually warmed to room temperature and stirred for 3 hours. The mixture was poured into ice-water. The organic layer was separated and washed in succession with 10% aqueous hydrochloric acid, water, a saturated aqueous solution of sodium bicarbonate, and brine. The organic solution was then dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated to dryness to yield 10.4 g (88%) of the desired product as a light brown oil.

EXAMPLE 516 1-[(4-Butylphenyl)methyl]-1-[6-(methylsulfonyloxy)hexyl]-3-(2,4,6-trichlorophenyl)urea

To a cooled solution (0°-5° C.) of 4.0 g of 1-[(4-butylphenyl)methyl]-1-(6-hydroxyhexyl)-3-(2,4,6-trichlorophenyl)urea and 2.6 ml of triethylamine in 90 ml of dichloromethane was added dropwise a solution of 0.8 ml of methanesulfonyl chloride in 10 ml of dichloromethane. The resulting solution was allowed to come to room temperature and was stirred for 16 hours. The procedure of Example 515 was continued and gave 4.5 g of the desired product as a light yellow oil in 97% yield

EXAMPLE 517 1-[(4-Butylphenyl)methyl]-3-(4-chloro-2-methylphenyl)-1-[6-[(methylsulfonyl)oxy]hexyl]urea

To a cooled solution (0°-5° C.) of 5.24 g of 1-[(4-butylphenyl)methyl]-3-(4-chloro-2-methylphenyl)-1-(6-hydroxyhexyl)urea and 4.0 ml of triethylamine in 65 ml of dichloromethane was added dropwise a solution of 1.2 ml of methanesulfonyl chloride in 10 ml of dichloromethane. The resulting solution was gradually warmed to room temperature, then was stirred for 16 hours. The procedure of Example 515 was continued and gave 6.0 g of the desired product as a light brown oil in 97% yield.

EXAMPLE 518 1-[(4-Butylphenyl)methyl-1-(6-cyanohexyl)-3-(2,4,5-trimethylphenyl)urea

A mixture of 2.0 g of 1-[(4-butylphenyl)methyl]-1-[6-[(methylsulfonyl)oxy]hexyl]-3-[(2,4,5-trimethylphenyl)methyl]urea, 0.5 g of sodium cyanide and 5.0 ml of dimethyl sulfoxide was heated at an oil bath temperature of 60°-70° C. for 1/2 hours. The mixture was cooled and poured into ice-water. The mixture was extracted with ether. The etheral layer was separated, washed with brine, dried over magnesium sulfate, and filtered. The filtrate was evaporated to dryness to yield 1.45 g (84%) of the desired product as a light brown oil.

EXAMPLE 519 1-[(4-Butylphenyl)methyl]-1-(6-cyanohexyl)-3-(2,4,6-trichlorophenyl)urea

A mixture of 2.2 g of N-[(4-butylphenyl)methyl]-N-[6-(methylsulfonyloxy)hexyl]-N-(2,4,6-trichlorophenyl)urea, 0.5 g of sodium cyanide, and 3.0 ml of dried dimethyl sulfoxide was heated at an oil bath temperature of 60°-70° C. for 20 hours. The mixture was poured into water and extracted with dichloromethane. The procedure of Example 518 was continued and gave 1.65 g (85% yield) of the desired product as a light brown oil.

EXAMPLE 520 1-[(4-Butylphenyl)methyl]-3-(4-chloro-2-methylphenyl)-1-(6-cyanohexyl)urea

A mixture of 2.0 g of 1-[(4-butylphenyl)methyl]-3-(4-chloro-2-methylphenyl)-1[6-[(methylsulfonyl)oxy]hexyl]urea, 0.5 g of sodium cyanide, and 3.0 ml of dimethyl sulfoxide was heated at an oil bath temperature of 60°-70° C. for 16 hours. The mixture was poured into water and extracted with dichloromethane. The procedure of Example 518 was continued and gave 1.5 g (88% yield) of the desired product as a brown oil.

EXAMPLE 521 1-(4-Butylphenyl)methyl]-1-(6-chlorohexyl)-3-(2,4,5-trimethylphenyl)urea

A mixture of 2.0 g of 1-[(4-butylphenyl)methyl]-1-[6-[(methylsulfonyl)oxy]hexyl]-3-[(2,4,5-trimethylphenyl)methyl]urea, 0.74 g of potassium chloride, and 4.0 ml of dimethyl sulfoxide was heated at an oil bath temperature of 60° C. for 12 hours. The mixture was cooled and poured into ice-water. The mixture was extracted with ether. The ether layer was washed with brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was evaporated in vacuo to yield 1.5 g of a light brown oil. The oil was purified by chromatography to yield 1.2 g of the desired product (68% yield) as a colorless oil.

EXAMPLE 522 1-[(4-Butylphenyl)methyl]-1-(6-chlorohexyl)-3-(2,4,6-trichlorophenyl)urea

A mixture of 1.9 g of 1-[(4-butylphenyl)methyl]-1-[6-[(methylsulfonyl)oxy]hexyl]-3-(2,4,6-trichlorophenyl)urea, 0.6 g of potassium chloride, and 3.0 ml of dried dimethyl sulfoxide was heated at an oil bath temperature of 60°-70° C. for 20 hours. The extraction and chromatography procedures of Example 521 were followed to give 1.1 g of the desired product as a colorless oil.

EXAMPLE 523 1-[(4-Butylphenyl)methyl]-1-(6-chlorohexyl)-3-(4-chloro-2-methylphenyl)urea

A mixture of 2.0 g of 1-[(4-butylphenyl)methyl]-3-(4-chloro-2-methylphenyl)-1-[6-[(methylsulfonyl)oxy]hexyl]urea, 0.74 g of potassium chloride, and 3.0 ml of dimethyl sulfoxide was heated at an oil bath temperature of 60°-80° C. for 16 hours. The mixture was diluted with water and extracted with dichloromethane. The organic layer was washed with three 40 ml portions of brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated in vacuo to yield 1.5 g of a brown oil. The oil was purified by chromatography to yield 1.5 g of the desired product as a light yellow oil in 86% yield.

EXAMPLE 524 1-[(4-Butylphenyl)methyl]-3-(2-hydroxy-5-methylphenyl)-1-[5-(trimethylsilyl)pentyl]urea

To an ice cold solution of 10 ml of borontribromide in dichloromethane is added dropwise a solution of 2.34 g of 1-[(4-butylphenyl)methyl-3-[(2-methoxy-5-methyl)phenyl]-1-[5-(trimethylsilyl)pentyl]urea in 20 ml of dichloromethane. The mixture is allowed to stir at room temperature for 24 hours, then is diluted with 50 ml of water and stirred for 3 hours. Two layers are separated. The organic layer is washed with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate is evaporated to dryness to yeild an oil. The oil is purified by Kugelrohr distillation to give the desired product.

EXAMPLE 525 1-[(4-Butylphenyl)methyl]-3-(4-carboxy-2-methyl)phenyl]-1-[5-(trimethylsilyl)pentyl]urea

A solution of 1.28 g of 1,-[(4-butylphenyl)methyl]-3-[(4-carboethoxy-2-methyl)phenyl]-1-[5-(trimethylsilyl)pentyl]urea in 30 ml of ethanol is treated with 5.0 ml of 1N sodium hydroxide. The resulting solution is stirred under reflux for 16 hours. The mixture is cooled and acidified with 1N hydrochloric acid. The precipitated solid is collected by filtration, washed with water, and dried. The desired product is crystallized from ethanol.

EXAMPLE 526 4-Butylbenzamide

To a stirred solution of 200 ml of aqueous ammonium hydroxide was added dropwise 35 ml of 4-butylbenzoyl chloride. The resulting mixture was stirred at room temperature for several hours. The white solid was collected by filtration, washed with water, then hexane, and dried in vacuo at 60° C. to give 33.4 g (99% yield) of the desired product, mp 135°-136° C.

EXAMPLE 527 4-Butylbenzenemethanamine

To a suspension of 15 g of lithium aluminum hydride in 200 ml of anhydrous ethyl ether under argon was added, at room temperature, a solution of 32.0 g of 4-butylbenzamide in 200 ml of freshly distilled tetrahydrofuran. The resulting mixture was stirred at room temperature for one hour and then heated at reflux for 20 hours. The mixture was cooled and sodium sulfate decahydrate was cautiously added portionwise to the mixture until it was colorless. The mixture was stirred for 30 minutes. The mixture was filtered and the filter was washed with ether. The filtrate was evaporated in vacuo to yield 29 g (99% yield) of a liquid. The liquid was distilled by Kugelrohr distillation, bp 85° C./0.070 mm of mercury, to give the desired product as a colorless liquid.

EXAMPLE 528 N-Heptyl-4-n-butylbenzamide

To a cold solution of 16 g of n-heptylamine and 29.0 ml of triethylamine in 300 ml of methylene chloride was added dropwise a solution of 27.4 g of 4-butylbenzoylchloride in 100 ml of methylene chloride. The resulting mixture was stirred at room temperature for 41/2 hours and diluted with water. The organic layer was washed with 1N sodium hydroxide, brine, dried, and evaporated. The residual solid was recrystallized from hexane to yield N-heptyl-4-n-butylbenzamide, mp 37°-38° C.

EXAMPLE 529 N-Heptyl-4-n-butylbenzenemethanamine

A solution of 38.0 g of N-heptyl-4-n-butylbenzamide and 280 ml of borane-tetrahydrofuran complex in 120 ml of anhydrous tetrahydrofuran was refluxed for 18 hours, allowed to cool, and treated with 6N hydrochloric acid. The organic solvent was evaporated and the residue was partitioned between ether and aqueous sodium hydroxide solution. The ether layer was separated, dried, and evaporated. The residue was distilled to yield N-heptyl-4-n-butylbenzenemethanamine as a colorless liquid, bp 115°C. at 80μ.

EXAMPLE 530 1-[(4-Butylphenyl)methyl]-1-(n-heptyl)-3-[2,4-difluorophenyl]urea

A solution of 1.55 g of 2,4-diflurophenylisocyanate in hexane was added to a solution of 2.61 g of N-heptyl-4-butylbenzenemethanamine in 15 ml of hexane and the solution was stirred at room temperature for 4 hours, then evaporated. The residual oil was distilled to yield 1-[(4-butylphenyl)methyl]-1-(n-heptyl)-3-[2 4-difluorophenyl]urea as a colorless oil, bp 160°-165° C./120μ.

EXAMPLE 531 N-[3,3-Dimethylbutyl]-4-n-butylbenzamide

To a solution of 4.94 g of 4-butylbenzoylchloride in 20 ml of methylene chloride was added dropwise a solution of 2.53 g of 3,3-dimethylbutylamine and 5.1 g of triethylamine in 80.0 ml of methylene chloride. The resulting mixture was stirred at room temperature for 18 hours. The mixture was diluted with water, and the organic layer was washed with 6N hydrochloric acid, water, 2N sodium hydroxide, brine, dried, and evaporated to dryness to yield an oil which solidified on standing. The solid was triturated with hexane, collected by filtration, and dried to yield N-[3,3-dimethylbutyl]-4-n-butylbenzamide as a white solid, mp 70°-71° C.

EXAMPLE 532

N-[3,3-Dimethylbutyl]-4-n-butylbenzenemethanamine

A solution of 7.5 g of N-[3,3-dimethylbutyl]-4-n-butylbenzenemethanamine in 40 ml of tetrahydrofuran was added dropwise to a suspension of 3.3 g of lithium aluminium hydride in 80 ml of tetrahydrofuran. The resulting mixture was refluxed for 18 hours, cooled, and the complex was decomposed by adding sodium sulfate decahydrate portionwise until a colorless mixture was obtained. The mixture was stirred for an additional half hour, filtered, and the filtrate was evaporated to dryness to yield a liquid. The liquid was distilled to yield N-[3,3-dimethylbutyl]-4-n-butylbenzenemethanamine as a colorless liquid, bp 80°-90° C at 80μ.

EXAMPLE 533 Phenyl-N-(4-chloro-2,6-dimethylphenyl)carbamate

A solution of 2.56 g of phenyl chloroformate in 20 ml of toluene was added to a cold solution of 2.47 g of 4-chloro-2,6-dimethylaniline and 2.4 ml of N,N-dimethylaniline in 80 ml of toluene. The resulting mixture was stirred at room temperature for 11/2 hours and then diluted with water The organic layer was washed with 3N hydrochloric acid, brine, dried, and evaporated. The residual solid was crystallized from ethylacetate:hexane to yield phenyl-N-(4-chloro-2,6-dimethylphenyl)carbamate, mp 158°-160° C.

EXAMPLE 534 1-[(4-Butylphenyl)methyl]-1-[3,3-dimethylbutyl]-3-[4-chloro-2,6-dimethylphenyl]urea

A solution of 825 mg of phenyl-N-(4-chloro2,6-dimethylphenyl)carbamate and 740 mg of N-[3,3-dimethylbutyl]-4-n-butylbenzenemethanamine in 40 ml of toluene was refluxed for 1 hour, cooled, and the solution was washed with 1N sodium hydroxide, brine, dried, and evaporated to dryness to yield a solid. The solid was recrystallized from hexane to yield 1-[(4-butylphenyl)methyl]-1-[3,3-dimethylbutyl]-3-[4-chloro-2,6-dimethylphenyl]urea as a white solid, mp 138°-139° C.

EXAMPLE 535 p-Neopentylbenzoic acid

To a cooled suspension of 43.0 g of anhydrous aluminum chloride in 250 ml of methylene chloride was added 40.0 g of oxalyl chloride over a period of 25 minutes. The resulting mixture was stirred for 5 minutes and then 43.2 g of neopentylbenzene was added dropwise maintaining a temperature of 0°-5° C. over a period of 35 minutes. The dark red mixture was stirred at an ambient temperature and then heated slowly to reflux for 3 hours, cooled, and poured into a mixture of 250 g of ice and 188 ml of concentrated hydrochloric acid. The mixture was stirred for 1/2 hour, and two layers were separated. The aqueous layer was extracted with methylene chloride and the combined organic layers were evaporated to yield a brown oily residue. The residue was heated and stirred under reflux with 200 ml of 10N sodium hydroxide, 150 ml of water, and 250 ml of ethyl alcohol for 20 minutes, cooled, and the mixture was extracted with ether. The aqueous layer was acidified with concentrated hydrochloric acid and stirred for 1 hour. The solid was collected by filtration, washed with water, dissolved in ethyl acetate, the aqueous layer was discarded, dried and evaporated to yield a solid. The solid was crystallized from acetone to yield p-neopentylbenzoic acid as a beige solid, mp 191°-193° C.

EXAMPLE 536 N-(3,3-Dimethylbutyl)-4-(2,2-dimethylpropyl)benzamide

To a cold solution of 5.26, g of 3,3-dimethylbutylamine and 21.0 ml of triethylamine in 180 ml of methylene chloride was added dropwise a solution of p-neopentylbenzoylchloride in 20 ml of methylene chloride. The resulting mixture was stirred at room temperature for 5 hours and diluted with water. The organic layer was washed with 3N hydrochloric acid, water, 1N sodium hydroxide, brine, dried, and evaporated to yield a solid. The solid was recrystallized from ethylacetate:hexane to yield N-(3,3-dimethylbutyl)-4-(2,2-dimethylpropyl)benzamide as a beige solid, mp 124°-126° C.

EXAMPLE 537 N-(3,3-Dimethylbutyl)-4-(2,2-dimethylpropyl)benzenemethanamine

A solution of 13.0 g of N-(3,3-dimethylbutyl)-4-(2,2-dimethylpropyl)benzenemethanamine in 50 ml of tetrahydrofuran was added dropwise to a suspension of 6.0 g of lithium aluminum hydride in 200 ml of tetrahydrofuran and the resulting mixture was heated to reflux for 18 hours, then cooled. The mixture was decomposed by adding sodium sulfate decahydrate portionwise until a colorless mixture was obtained. The mixture was stirred for an additional half hour, filtered, and the filtrate was evaporated to yield an oil. The oil was distilled to yield N-(3,3-dimethylbutyl)-4-(2,2-dimethylpropyl)benzenemethanamine as a colorless oil, bp 100°-110° C at 100μ.

EXAMPLE 538 1-[3,3-Dimethylbutyl]-1-[[4-(2,2-dimethylpropyl)phenyl]methyl]-3-[4-chloro-2,6-dimethylphenyl]urea

A solution of 825 mg of phenyl-N-(4-chloro-2,6-dimethylphenyl)carbamate and 782 mg of N-(3,3-dimethylbutyl)-4-(2,2-dimethylpropyl)benzenemethanamine in 40 ml of toluene was heated to reflux for 1 hour, cooled, and the solution was washed with 1N sodium hydroxide, brine, dried, and evaporated to dryness to yield a solid. The solid was recystallized from hexane to yield 1-[3,3-dimethylbutyl]-1-[[4-(2,2-dimethylpropyl)phenyl]methyl]-3-[4-chloro-2,6-dimethylphenyl]urea as a white solid, mp 148°-150° C. 

I claim:
 1. Compounds of the formula: ##STR8## wherein X represents one or more substituents selected from the group consisting of fluoro, chloro and methyl and Y is alkyl(C₄ -C₆) or alkoxy(C₄ -C₆).
 2. The compound according to claim 1; 1-(n-heptyl)-1-(4-neopentylbenzyl)-3-(2,4-difluorophenyl)urea.
 3. The compound according to claim 1; 1-(n-heptyl)-1-(4-neopentylbenzyl)-3-(4-chloro-2,6-dimethylphenyl)urea.
 4. The compound according to claim 1; 1-(n-heptyl)-1-(4-neopentylbenzyl)-3-(2,4-trifluorophenyl)urea.
 5. The compound according to claim 1; 1-(n-heptyl)-1-(4-isoamylbenzyl)-3-(2,4-difluorophenyl)urea.
 6. The compound according to claim 1; 1-(n-heptyl)-1-(4-isoamylbenzyl)-3-(2,4,6-trifluorophenyl)urea.
 7. The compound according to claim 1; 1-(n-heptyl)-1-(4-isoamylbenzyl)-3-(4-chloro-2,6-dimethylphenyl)-urea.
 8. The compound according to claim 1; 1-(n-heptyl)-1-(4-n-butylbenzyl)-3-(2,4-dimethylphenyl)urea.
 9. The compound according to claim 1; 1-(n-heptyl)-1-(4-n-butoxybenzyl)-3-(2,4-dimethylphenyl)urea. 